Clinical Reviews in Bone and Mineral Metabolism

, Volume 15, Issue 4, pp 162–174 | Cite as

A Review on Bone Mineral Density Loss in Total Knee Replacements Leading to Increased Fracture Risk

Open Access
Review Paper

Abstract

The link between low bone mineral density (BMD) scores leading to greater fracture risk is well established in the literature; what is not fully understood is the impact of total knee replacements/revisions or arthroplasties on BMD levels. This literature review attempts to answer this question. Several different databases using specific key terms were searched, with additional papers retrieved via bibliographic review. Based on the available evidence, total knee replacements/revisions and arthroplasties lower BMD and thus increase fracture risk. This review also addresses the possible implications of this research and possible options to reduce this risk.

Keywords

Total knee replacement TKR Fracture risk Bone mineral density BMD 

Introduction

Two of the predominant pathological disorders that affect bone mineral density (BMD) are osteoarthritis (OA) and osteoporosis (OP). Due to the destructive nature of OA on the joints and the resulting loss of mobility and function, surgery is a primary option, and as such, OA accounts for between 80 and 90% of all total knee replacement (TKR/arthroplasty) procedures [1, 2, 3, 4, 5].

The relationship between OA and OP is complex and has been reported to be an inverse one [6], with OA being reported to increase BMD, and thus, it might be assumed to increase fracture protection. With such a high percentage of cases of TKR due to OA, it could be concluded that this protective effect would reduce fracture risk in TKR patients due to having higher BMD, but increased fracture rates have also been reported in OA. A narrative literature review was conducted to investigate the links between BMD, OA, and fracture risk in TKR; these specific key terms were searched in different combinations across the databases: PubMed, Google Scholar, Web of Science and Embase, with additional papers retrieved via bibliographic review.

The Relationship Between BMD and OA

Research on the relationship between OA, BMD and the subsequent fracture risk has produced many controversial and conflicting results.

In 1972, Foss et al. were the first to observe the correlation between OA and fracture risk, concluding that patients with OA had a greater BMD for their age and thus had fewer hip fractures [6]. This suggested the possibility of a protective effect of OA due to higher BMD, with several studies supporting the link between OA and higher BMD (as shown in Table 1); Dequeker et al. in 2003 reviewed the relationship between increased severity of OA resulting in higher BMD scores, discovering 36 previous studies across 16 countries (Europe, the USA and Australia) covering a total of 37,774 subjects including 11,137 OA cases. Twenty-eight of these studies showed an increase in BMD with the remaining eight studies showing there was no increase in BMD [9].
Table 1

Studies showing BMD related to OA

Name of study

Participant numbers

Type of study

Type of OA if stated

Had OA

OA diagnosis

Comparator

BMD measurement site

Result

Arokoski et al. (2004) [7]

57

Not stated

27

Based on the American College of Rheumatology criteria regarding classification of OA in the hip

30 age matched controls

BMD and bone mineral content (BMC) measurements of the hip; femoral neck and head

Hip OA is not associated with an increase of BMD in the femoral neck or in the head of the femur

Chaganti et al. (2010) [8]

3923

Cohort study with cross-sectional analysis

Two distinct radiographic hip OA (RHOA) phenotypes: osteophytic and atrophic were examined

209 grade ≥ 2

185 grade 3–4

RHOA hip radiographs were assessed for five individual radiographic features of OA: joint space narrowing (JSN), osteophyte formation, cysts, subchondral sclerosis and femoral head deformity. Graded on severity 0–4

No RHOA (grade 0–1)

Lumbar spine, femoral neck, total hip and trochanteric sites

Both moderate and severe RHOA groups had significantly higher areal BMD at all BMD sites compared to the control group with no RHOA

Dequeker et al. (2003) [9]

37,774 across 36 papers

Meta-analysis

11,137

Not stated

26,637 controls

Not stated

28 papers showed an increase in BMD and 8 showed no increase

Hart et al. (2002) [10]

830

Cross-sectional

115 had baseline OA, of which 33 progressed to osteophytes after 4 years. Of the remaining 715, 95 had incident knee osteophytes within 4 years

Radiographic OA (ROA) on knee and hand x-rays, based on JSN and presence of osteophytes and thus graded on severity

No OA

Lumbar spine and hip

The 95 women with incident knee osteophytes had significantly higher baseline spine BMD and significantly higher hip than those without incident disease

Lethbridge-Cejku et al. (1996) [11]

649

Not stated

649 (240 grade 0, 186 grade 1, 187 grade 2, 35 grade 3, 1 grade 4)

Radiographs were read for features of OA using Kellgren Lawrence (KL) and reliable individual feature scales

No OA (grade 0–1)

Lumbar spine and hip

These results show that both men and women with radiographic changes of knee OA, specifically osteophytosis, have higher levels of adjusted spine but not hip BMD

Nevitt et al. (1995) [12]

4855

Cross-sectional

351 (grade 2), 228 (grade 3–4)

Radiographic OA on pelvis x-rays looking at hip features: osteophytes, JSN, subchondral sclerosis, cysts and femoral head deformity graded on severity

No OA

Femoral neck, trochanter, lumbar spine, calcaneus and distal radius

Elderly Caucasian women with moderate to severe radiographic hip OA had higher BMD in the hip, spine and appendicular skeleton than did women without hip OA

A study by Hart et al. [10] showed 95 women had a higher hip and spine BMD versus controls (0.79 versus 0.76 g/cm2, or 3.9%, and 1.01 versus 0.95 g/cm2, or 6.3%, for the hip and spine respectively); this itself is supported by other research [12] that concluded that OA resulted in higher BMD in the hip and spine, than women without hip OA. This trend was also seen in elderly men, who showed higher BMD in both the lumbar spine and hip compared to age-similar matched controls without OA [8]. This is further validated by research that shows an increase in BMD of the spine of patients with OA compared to controls [11, 13, 14].

There is research that states that although spine BMD might be high, hip BMD was not, as investigated by Lethbridge-Cejku et al. [11] who recruited 402 men and 247 women with OA. The results showed high levels of spine BMD but not hip BMD; this is supported by Arokoski et al. [7] whose findings suggest that hip OA is not associated with an increase of BMD in the femoral neck or in the head of the femur. It must be stated that there is also a small amount of research contrary to this that states OA lowers BMD compared to controls [15].

The majority of the research shows an increase in BMD in OA patients [6, 10, 11, 12, 13, 14, 16], but it must be acknowledged that there are other factors in OA; the phenotypes within OA such as osteophytic (which is osteophyte predominant [8]) and atrophic (which is joint space narrowing (JSN) predominant) both influence BMD scores. Out of the papers mentioned, only the Chaganti et al. study directly referred to the phenotypes’ impact; they showed significant differences in the hip and lumbar spine of areal BMD (aBMD) measurements for the two radiographic hip OA (RHOA) phenotypes compared to the control group. The osteophytic RHOA group had a higher aBMD at all sites compared to the control group: + 3.9% at the total hip (p = 0.002), + 8.5% at the femoral neck (p < 0.0001), + 4.6% at the trochanter site (p = 0.002) and + 7.2% at the lumbar spine (p = 0.0003). In contrast, the atrophic phenotype was not significantly associated with any difference in aBMD compared to controls [8]. The other studies mainly graded OA on a combination of factors resulting in a severity score; as such, these results might not be universal and may be more likely associated with the osteophytic phenotype. This is further supported by research that showed that obese patients have a more osteophyte dominant OA pattern compared to non-obese patients, 74.5% compared to 34.8% [17]; this coupled with increasing obesity in the population and the association of obesity with the onset and progression of OA in the knee [18] resulting in more TKRs might reflect the associated BMD changed and OA diagnosis.

Due to this recorded increase in BMD, it is generally thought that this would translate to having a protective effect on the bone by reducing fracture risk. This does not seem to be the case as several studies have argued against the protective nature of OA and actually demonstrate an increase in fracture risk (as shown in Table 2). Reasons for this contradiction in correlation could be due to limitations in the DXA scans only measuring two dimensions and not accounting for bone depth [25]. Furthermore, research has demonstrated that osteophytes contribute between 16.6 and 22% of the lumbar spine BMD variation in DXA scans in women and men respectively [26], possibly leading to an overestimation of higher BMD without the increase in bone strength; this might also explain the osteophyte phenotype predominance BMD results shown by Chaganti et al.
Table 2

Studies showing negative results between OA and fracture risk

Name of study

Participant numbers

Type of study

Had OA

OA diagnosis

Comparator

BMD measurement site

Result

Arden et al. (1996) [19]

937 (92 fractures)

Case-control study

319 with OA

OA was classified radiologically using standard x-rays of the pelvis, thoracolumbar spine, hands and weight-bearing knees. Radiographs were scored to the KL method

618 no OA

Lumbar spine and femoral neck

Despite having increased BMD of 5.3%, subjects with hip OA had a significantly increased risk of fracture compared to controls

Arden et al. (2006) [20]

6641

Randomised control trial

422 with OA and 277 with prevalent OA (clinically diagnosed)

The knee pain and OA questionnaire. They were also asked if they had ever received a clinician diagnosis of knee OA: “Has a doctor ever told you that you have OA of the knee?”

No knee OA 5774 (clinically diagnosed)

BMD not recorded

Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of non-vertebral and hip fracture

Bergink et al. (2003) [21]

4239

Cohort study

1466 fracture group contains 320 OA cases

ROA was assessed by means of the KL grading system in 5 grades (from 0 to 4)

2773 non-fracture group contained 675 OA cases

Lumbar spine and femoral neck

Although people with ROA had a higher BMD, their incident fracture risk was increased as compared with those without ROA

Chan et al. (2014) [22]

3864

Population-based prospective study

1077 with OA 325 fractures

The presence of OA was ascertained at baseline by self-reported diagnosis

1787 no OA 745 fractures

Lumbar spine and femoral neck

Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA

Jones et al. (1995) [23]

1821

Longitudinal population-based study

462 with OA

Medication use and self-reported arthritis were assessed by a structured personal interview

1359 no OA

Lumbar spine and femoral neck

Individuals with self-reported OA, despite higher BMD, are not protected against non-vertebral osteoporotic fracture

Lee et al. (2014) [24]

1829

Cross-sectional study

34.20%

Radiographic knee OA was defined as KL grade ≥ 2

65.80%

Lumbar spine and femoral neck

In both sexes, the prevalence of vertebral fractures increased with age and was higher in the knee OA group than in the control group (in men, 13.2% in the OA group and 7.9% in the control group; in women, 27.7% in the OA group and 14.7% in the control group)

This bone strength argument is further supported by Lee et al. [24] whose cross-sectional study proposed that despite OA subjects having high systematic BMD, they were positively associated with vertebral fractures. Lee et al. suggested that bone quality, and consequently bone strength, may be decreased at the systemic level in knee OA, resulting in a higher risk of fracture [24]. A similar idea is shared by Ding et al. [27] whose research looked at OA in post-mortem participants, using microcomputed tomography scans of the microarchitecture of the proximal tibiae. This showed that medial OA trabecular bone was significantly denser but had poorer mechanical properties than normal bone. Ding et al. suggested that bone remodelling in OA leads to deterioration in architecture, resulting in poor quality bone, so although BMD could be retained, the bone quality was less, resulting in the possibility of greater fracture risk. This effect might be explained due to subjects with OA having a greater proportion of undermineralisation (immature matrix) in the bone [28]. This rationale is further supported by some research suggesting that bone trabecular microarchitecture was the key determinant of fractures in addition to the BMD data [29].

It must be stated that bone quality is affected by many other factors, not only the influence of OA. This includes factors such as obesity (which results in an increased risk of OA [22, 30]), diabetes and chronic kidney disease (CKD). Obesity is associated with higher BMD [31] but has been reported to lead to a lower rate of bone formation [32]. Type 2 diabetes is associated with higher BMD, but increased overall and hip fracture risk [33]. Research has shown that this might be due to changes in bone material properties rather than BMD, such as bone strength, structure, and quality, encompassing the microstructural and tissue material properties [34]. CKD can influence bone quality by altering bone turnover and mineralisation, resulting in microdamage and structural and material changes [35].

As shown in Table 2, several studies have argued against the protective nature of OA, reporting an increase in fracture risk despite subjects having increased BMD. One study reported a BMD increase of 5.3% compared to controls but no reduction in fracture risk [19]; this is further supported by the Rotterdam study [21] which utilised 2773 subjects and concluded that patients with knee OA had an increased risk of both vertebral (2.0-fold) and non-vertebral (1.5-fold) fractures. Furthermore, individuals with self-reported OA also had higher BMD but were not protected against non-vertebral osteoporotic fracture [23].

A study in 2014 [22] also demonstrated an increase in fracture rate among OA patients, in which 3864 subjects aged > 45 years were analysed. Results revealed that fracture risk was significantly higher in women with OA than those without OA. A prospective randomised control trial conducted by Arden et al. supports this argument where over 6500 men and women ≥ 75 years were recruited over 3 years, concluding that patients with knee pain and knee OA had an increased risk of non-vertebral and hip fracture [20].

It must be acknowledged that some studies have supported the idea of the OA protective effect; for example, Vestergaard et al. [36] conducted a case-control study using over 24,655 fractures matched for age and gender, with the main exposure being OA; their research showed that OA seemed to be associated with a decreased risk of fractures in multiple skeletal sites. This is agreed upon by Cumming and Klineberg [37] who had 189 participants (65–79 years old) with self-reported OA; the subjects with OA had fewer reported hip fractures than randomly assigned controls (4% compared to 13%). Additionally, Cumming et al. showed an inverse association between the number of joints reported to be affected by OA and the risk of hip fracture, with this protective effect being reported in both women and men [37].

Other research has shown a lack of any relationship between OA and fracture risk despite increased BMD [23, 38], with additional research using cohort studies showing no relationship between fracture risk and OA [39], contributing to the theory that OA does not have a protective effect on fracture risk.

Due to the contradiction and failure of the observed increase in BMD to translate into a protective effect and reduce fracture risk, several rationales were investigated. One rationale as to why an increased fracture risk may be explained, in part, was due to an increased fall tendency in patients with OA [38]. Research has shown that people with knee or hip OA have a greater number of falls and fracture risk compared to the general population [40, 41], even showing an increase in odds of falling correlated to the number of affected joints with OA [41].This theory is shared by other research [42], with some stating this is due to OA causing worsened postural stability and thus increasing the tendency to fall [23]. This is contradicted however by two cohort studies [20, 38] that reported that increased risk of fracture was independent of the number of falls. Although this in itself may be explained due to the severity of the falls and not the number of falls [20]. However, this rationale may be difficult to justify as fall data is often incomplete [43].

DXA bone density measurement provides an incomplete picture of bone strength as it is derived from the bone mineral content (BMC) divided by bone area, but does not account for the distribution of the trabeculae and the structural integrity of the microarchitecture. Bousson et al. created a tool called the trabecular bone score (TBS) [44] which is able to differentiate between microarchitectures that exhibit the same density [44]. This new method was investigated by Hopkins et al. [45] who recruited 19 post-menopausal women prior and post-TKR. The results exhibited that participants with TKR had higher mean lumbar BMD scores compared to controls but a lower TBS, suggesting that OA is potentially concealing poorer bone quality, even though it has a higher BMD. A further study by Hopkins et al. investigated differences in bone quantity and quality assessed by spine BMD and TBS [46]. These results demonstrated that the participants with TKR had higher BMD than the controls but poorer TBS scores [46].

TBS and BMD at the lumbar spine suggests that the generally higher BMD typically observed in OA patients may be disguising poor quality bone with less structural integrity [45]; this is supported by the rationale and results of the previous studies mentioned [24, 27] and might be the main reason that OA with high BMD does not a have protective effect in reducing fracture risk.

BMD, Fracture and TKR Relationship

The relationship between low BMD and increased fracture risk is well recognised [47, 48, 49, 50, 51, 52], but the association between BMD scores, TKR and the associated fracture risk is not well established.

The majority of the research shows a loss of BMD after a TKR (arthroplasty) (Table 3); Gazdzik et al. [54] reported a decrease in BMD 12 months after TKR surgery with the most significant BMD decrease during the period of 5–12 weeks after the surgery at the periprosthetic region. Other research concurs with this, stating the greatest loss of periprosthetic BMD has been observed within the first 3 months (12 weeks) after surgery [61, 62, 63], with some research reporting a temporary BMD loss of 13% at the proximal tibia [57].
Table 3

Studies showing BMD changes after knee arthroplasty

Name of study

Participant numbers

OA diagnosis if stated

Place BMD measured

Comparator

Intervals BMD measured

Result

Beaupre et al. (2015) [53]

97

Total hip and spine BMD

Pre-op BMD measurements

12 months post-operatively

Subjects undergoing primary cemented TKA had significant bone loss in the hip within 12 months, beyond that expected with age

Gazdzik et al. (2008) [54]

106

BMD measured in 4 regions around the knee

Baseline (first post op scan)

Before surgery, 2 weeks post-surgery (baseline), 5, 12, 24, 48 weeks

The most significant BMD decrease was observed in the period between 5 and 12 weeks after the TKA

Hopkins et al. (2016) [45]

62

28% of the controls had OA, and 86% of the testing group had OA

BMD measurements at the neck of the femur, total hip region and lumbar spine

46 age matched controls and non-operated hip

Pre-surgery baseline, and at 6 weeks, 6 months and 12 months post-surgery

Following surgery, an immediate loss of ipsilateral bone mass at the TH and NOF was demonstrated which was not restored at 12 months

Ishii et al. (2000) [55]

24 (31 knees, 47 hips)

All patients had the preoperative diagnosis of OA

BMD measurements of the hip

Non-operated hip

BMD measured preoperatively and a mean follow-up 48 months

Despite a predicted age-related loss of 4% during 2 years, 45% of the hips on the operative side and 59% of the hips on the non-operative side had BMD higher than preoperative levels. Of the hips, 81% on the operative side and 82% on the non-operative side had BMD that was within the expected 4% age-related loss

Kim et al. (2014) [56]

48

TKA was performed with patients who had a radiographic KL grade 3 or greater. Non-operative side had KL grade 2 for 40 patients and grade 3 for 8

BMD measured at femoral neck trochanter and total hip

Non-operated hip

Measurement of BMD was performed preoperatively and 1, 3 and 6 months and 1 year after unilateral TKA

Preoperatively, BMD of the femoral neck, trochanter and total hip on the operative side were lower than those on the non-operative side; however, there was no statistical difference

Li et al. (2000) [57]

28

BMD measured around proximal tibia measured at 9 regions

Baseline (first post op scan)

1 week after the operation (baseline); measurements were repeated at 3, 6, 12 and 24 months

The mean bone mineral density of all 9 regions of interest at the proximal tibia temporarily decreased by 13%

Liu et al. (1995) [58]

48

14 with knee OA

BMDs of both knees

20 age matched controls

Both knees were measured before operation and then at 3, 6 and 12 months after operation

The preliminary results demonstrate a significant progressive decrease of BMD in the distal femur of the operated knees after TKA, whereas the BMD of the non-operated knees remains stable

Petersen et al. (1995) [59]

25 (25 knees)

All had primary arthritis

BMD measured under the tibial component 6 regions

Baseline (first post op scan)

BMD measurements were performed within 2 weeks after the operation and at follow-up after 6 months and 1, 2 and 3 years

On average, the density for all regions of interest below the tibial component showed a significant and progressive decrease in BMD, reaching 22% at 3 years follow-up

Soininvaara et al. (2004) [60]

69

All patients had OA knees. The severity of OA was classified from preoperative standing x-rays using Ahlback’s classification

Hip and contralateral BMD measurements divided into regions

Non-operated side

At the time of operation (baseline) and at 1 year after operation

In all regions of interest, the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side

This BMD loss is further supported by a study by Kim et al. [56] who investigated 48 Korean patients (11 males, 37 females, mean age 63 years) post-TKR; they reported a significant decrease in BMD at the trochanters and femoral neck in the first 3 months post-surgery, followed by a recovery of the BMD losses to − 2.14% at 12 months. A similar trend is seen across the research by Ishii et al. [55], Hopkins et al. [45] and Petersen et al. [59] who all reported a decrease in total hip BMD during the first 6 months post-operatively.

Other research investigated the effects of TKR 12 months post-operatively. Beaupre et al. [53] conducted a cohort study across 12 months and demonstrated that BMD decreased significantly by 1.80% at the total hip over that time. Soininvaara et al. [60] measured the BMD of bilateral hips in 69 patients undergoing total knee arthroplasty (TKA) (20 males, 49 females, mean age 67 years). They found a decrease in BMD at 12 months post-operatively of up to 2.7% per year in the ipsilateral hip and up to 1.18% per year in the contralateral hip; this bone loss affecting the operated side more than the non-operated has been seen in other studies [58]. Mintzer et al. [64] reported that within the first 12 months post-operatively, 68% of patients had radiographic evidence of bone loss at the distal anterior femur. There are many more studies that have shown a correlation between TKR (arthroplasty) and BMD loss [59, 65, 66, 67, 68, 69, 70], although there are some studies that dispute this association and have shown no change in BMD post-TKR/A [57, 71, 72], with some research actually showing a small increase [73].

It is argued that BMD recovers to a baseline by 2 years [74], with research showing the greatest loss is within the first 2 years and eventually stabilising at that point [75], although this in itself has been contested [57, 76]. One explanation for this decline in BMD is a reduction in mobility of the patient post-surgery leading to reduced weight bearing and thus disuse related bone loss [64, 77]; this potentially explains the trend of such significant BMD reductions in the first 6 months and levelling out at 2 years post-operatively [55].

Due to the majority of papers reporting a significant loss of BMD post-TKR/A, the possible associated fracture risk must be investigated (this is shown in Table 4). A study by Meek et al. reported that women aged ≥ 70 years who had a TKR were 1.6 times more likely to have a fracture than younger patients and 2.3 times more likely to suffer a fracture than men [78]. This is further supported by Toogood et al. who stated that the greater majority of annual periprosthetic fractures were more often elderly and female [79]. Preliminary results from the Sahlgrenska Academy in Mölndal [80] analysed medical records from 1987 to 2002, concluding that individuals who had a TKR had an increased risk for hip fracture by 4%, with the risk for vertebral fracture increasing by 19% compared to the population without TKR.
Table 4

Studies showing fracture risk with TKR

Name of study

Participant numbers

Result

Lalmohamed et al. (2012) [42]

6763 cases (89 had knee arthroplasties (KA)), 26,341 controls (208 had a KA)

A 54% increased hip fracture risk was found in patients who underwent KA

Meek et al. (2011) [78]

44,511 primary TKRs and 3222 revision TKRs

Comparison of survival analysis for all primary and revision arthroplasties showed periprosthetic fractures were more likely in females, patients aged > 70 and after revision arthroplasty

Prieto-Alhambra et al. (2011) [43]

20,033 knee OA (cases) 100,065 (controls)

Hip fracture rates were non-significantly reduced compared with controls before the operation. In the year after TKR, risk increased significantly

Toogood et al. (2015) [79]

30,624 (total joint arthroplasty, TKA and total hip arthroplasty)

Individuals admitted with periprosthetic fracture were older, were more often female, were more often admitted emergently

Vala et al. (2016) [80]

The research followed the total Swedish population born 1902–1952 (n = 4,546,820) during the period 1987–2002 resulting in a total of 3719 having TKR and a fracture

After total knee replacement, the risk for hip fracture increased by 4% and the risk for vertebral fracture increased by 19% compared to the population without TKR

The Prieto-Alhambra et al. [43] research supports this increase in hip fracture after TKR reporting that hip fracture rates were insignificantly reduced compared to controls before the operation, but within 12 months post-operatively, TKR patients had a higher rate of hip fracture than controls, with relative risk increasing significantly up to 1.58 and then declining to equal the controls by 3 years. Additional research [42] has also shown a relationship between TKA and fracture risk, reporting a 54% increased risk of hip fracture, in particular among adult patients aged 71 years old, with the increase risk of hip fracture greatest after the first few years. Other research has shown an even higher figure, reporting a 58% increase in hip fracture in patients who had undergone TKR [43].

This increase in fracture risk during the first few years is time-dependent and as such could be associated with the evidence that supports early BMD decline as an important predisposing factor contributing to fracture risk [81, 82, 83, 84, 85].

There are other reasons put forward for the increased fracture risk in TKR patients, with some reports stating there is a higher incidence of falls thus a higher chance of fracture. Research by Matsumoto et al. [86] reported that of 81 patients who underwent TKA, the incidence of falls was 38% in the first year post-operatively, compared to 24% in the non-TKA cohort. Additional research also shows a higher rate of falls indicating scores of between 23 and 43% [87, 88, 89, 90]. Although some research contradicts this and shows fall incidences were not significantly higher in the TKR group [45].

One possible intervention is antiresorptive treatment. Hahn and Won [72] investigated this, concluding that bisphosphate treatment just after TKR surgery prevented early BMD reduction in the hip and would be beneficial in the prevention of later hip fracture. This is supported by research by Carulli et al. [91], who proposed the use of bisphosphonate treatment in patients to not only prevent bone loss but increase implant survival. Other studies [92] reviewed the effectiveness of bisphosphonate use on post-TKR fracture risk recruiting patients who had received a TKR between 1986 and 2006 for knee OA. They concluded that bisphosphonate treatment after a TKR reduced the risk of fracture by 50–55%. Additionally, a meta-analysis [93] in 2015 reviewed the long-term effects in using bisphosphonates, reporting a significant decrease in implant revision after TKA or total hip arthroplasty (THA). Although caution should be utilised when administering bisphosphonates for long-term use, as research from 2017 has recently reported an increase in the size and number of microcracks leading to higher fracture risk in those patients on long-term bisphosphate use [94]. Furthermore, there have been reports of long-term use leading to increased atypical femoral fractures [95].

Some studies have looked at other possible antiresorptive treatments, such as hormone replacement therapy (HRT) to reduce BMD loss; several studies have shown an increase in BMD at all skeletal sites in early and late post-menopausal women [96, 97] with studies reporting a BMD increase of 5.3% at the lumbar spine and 7.6% at the femoral neck compared to 0.2 and 2.1%, respectively, in the control placebo group [98], although it must be noted that long-term use of HRT is strongly associated with breast cancer [99], so long-term administration is no longer advisable [100].

Other possible antiresorptive treatments are selective oestrogen receptor modulators (SERM); these have been reported to show an increase in BMD in the femoral neck by 2.1–2.4% and in the spine by 2.6–2.7% compared to placebo controls [101]. Unfortunately, there are obstacles to SERM such as causing menopausal symptoms (breast pain, hot flushes) and resulting in an increase in thromboembolic events [102, 103].

In contrast to antiresorptive treatments, there are also anabolic agents; these stimulate bone growth, with currently the only approved anabolic for systemic use being parathyroid hormone (PTH) [104]; this treatment stimulates osteoblasts, thus promoting increased BMD, although PTH has been associated with side effects such as headaches, dizziness, joint pain, depression [105] and hypercalcemia [106]. Another anabolic treatment investigated was strontium ranelate [104]; this treatment is capable of encouraging bone growth via stimulating osteoblast activity [107]. This drug was withdrawn in 2017 [108] due to safety concerns such as cardiovascular risks and increase risk of death [109].

Other research has investigated the selection of materials, design and alignment of joint components for replacements and how these might impact BMD [110, 111]. These mainly come in the form of metal implants and can be used in both tibial and femoral defects regardless of cementation.

These implants are primarily chosen due to being bioinert, able to support mechanical loads and being highly porous, promoting osteointegration [112]. Research has shown that tantalum cone implants were fully integrated after 2 years [113] and have been reported to maintain tibial bone density [114]; together with the material tantalum, porous titanium cones that mimic normal trabecular bone have been investigated; this type of implant has been shown to increase BMD at particular regions by 8.1% [115], with further research showing a similar favourable effect on BMD [116]. Some research however demonstrates that there is no significant difference in changes in BMD between the groups [117]. The titanium cone implants have also shown to have better stability than their tantalum counterparts [118]. In addition to the cones, some studies have investigated the effect of hydroxyapatite (a bioceramic that resembles the mineral constitutes of human bones and teeth [119]) coated onto the titanium implants to promote ingrowth; this combination has shown to increase shear strength [120] but has been reported to lead to decreased bone formation on porous coated titanium [121].

Metaphyseal sleeves have also been investigated; these come in a variety of different shapes and are press fitted into bone allowing bony ingrowth; research has reported excellent osteointegration and lasting fixation [122], showing ingrowth stability 3 months post-operation [123]. Unfortunately, there appears a lack of data about metaphyseal sleeves in TKR/A affecting BMD, with the main priority being stabilisation and survivorship.

Conclusion

Low BMD has long been associated with an increased fracture risk, and the majority of the research shows that TKR results in reduced BMD, with potential increased fracture risk for the first 2 to 3 years. As such, it is suggested that patients with low BMD should be treated in order to combat this either through antiresorptive therapies, anabolic treatments or particular specialised implants prior to surgery in order to reduce this risk. The influence of low BMD does not only affect the patient; 60% of orthopaedic surgeons have stated that low BMD would influence their surgical plan and the implant design, yet only 4% performed BMD measurements preoperatively [124]. This is suggested by other research and states that surgeons must consider BMD loss if they are relying on bone for long-term stable fixation of the prosthesis [70].

In cases of patients with reported OA, their BMD measurements should utilise an additional type of measurement in addition to the DXA scan, either TBS or other means of assessment in order to assess bone architecture. TBS itself has started to be recognised and has been used in osteoporosis diagnosis with further suggestion for it to be used as a tool to monitor treatment effects [125]. This assessment would all be in addition to clinical risk factors that contribute to fracture risk independently of BMD including age, previous fragility fracture, premature menopause, a family history of hip fracture and the use of oral corticosteroids [126].

Finally, it must be noted, for the associated risks of fracture with TKR/A, the impact on quality of life for the patient is paramount. Research has shown that those undergoing a TKR due to high risk of knee OA have an improved quality of life compared to those who do not get a TKR [127, 128]. Furthermore, TKA has shown to have high patient satisfaction and long-term survival [129].

Notes

Funding

This work will form part of the authors (Michael Gundry) PhD thesis in medical imaging which was part funded by the Stryker Institute with research investigating changes in BMD in bone surrounding cone implants on TKR revision patients.

Compliance with Ethical Standards

Disclosures

Author Michael Gundry’s current PhD is in part funded by the Stryker Institute with research investigating changes in BMD in bone surrounding cone implants on TKR revision patients. There is no grant number, but it is stated as an industry-funded, non-commercial study subject to a Masters Service Agreement between Stryker UK and the Royal Devon and Exeter Hospital. Additionally, authors Knapp and Hopkins have no conflict of interest to declare.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Lohmander SL. Knee replacement for osteoarthritis; facts, hopes, and fears. Medicographia. 2013;35(2):181–8.Google Scholar
  2. 2.
    Koskinen EA, et al. Comparison of survival and cost-effectiveness between unicondylar arthroplasty and total knee arthroplasty in patients with primary osteoarthritis: a follow-up study of 50, 493 knee replacements from the Finnish Arthroplasty Register. Acta Orthop. 2008;79(4):499–507.PubMedGoogle Scholar
  3. 3.
    Knutson K, Lewold S, et al. The Swedish knee arthroplasty register. A nation-wide study of 30,003 knees 1976–1992. Acta Orthop Scand. 1994;65(4):375–86.PubMedGoogle Scholar
  4. 4.
    Hawker G, Wright J, et al. Health-related quality of life after knee replacement. J Bone Joint Surg Am. 1998;80(2):163–73.PubMedGoogle Scholar
  5. 5.
    National Institute for Health and Care Excellence. Osteoarthritis: care and management in adults clinical guideline [CG177]. 2014. https://www.nice.org.uk/Guidance/CG177. Accessed 24 March 2017.
  6. 6.
    Foss MVL, Byers PD. Bone density, osteoarthritis of the hip, and fracture of the upper end of the femur. Ann Rheum Dis. 1972;31:259–64.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Arokoski JPA, Arokoski MH, et al. Estimation of femoral head bone density using magnetic resonance imaging: comparison between men with and without hip osteoarthritis. J Clin Densitom. 2004;7(2):183–91.PubMedGoogle Scholar
  8. 8.
    Chaganti RK, Parimi N, et al. Bone mineral density and prevalent osteoarthritis of the hip in older men for the Osteoporotic Fractures in Men (MrOS) Study Group. Osteoporos Int. 2010;21(8):1307–16.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Dequeker J, Aerssens J, et al. Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res. 2003;15(5):426–39.PubMedGoogle Scholar
  10. 10.
    Hart CC, et al. The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: the Chingford study. Arthritis Rheum. 2002;46(1):92–9.PubMedGoogle Scholar
  11. 11.
    Lethbridge-Cejku M, Tobin JD, et al. Axial and hip bone mineral density and radiographic changes of osteoarthritis of the knee: data from the Baltimore Longitudinal Study of Aging. J Rheumatol. 1996;23(11):1943–7.PubMedGoogle Scholar
  12. 12.
    Nevitt MC, Lane NE, et al. Radiographic osteoarthritis of the hip and bone mineral density. The Study of Osteoporotic Fractures Research Group. Arthritis Rheum. 1995;38(7):907–16.PubMedGoogle Scholar
  13. 13.
    Hochberg MC, Lethbridge-Cejku M, et al. Bone mineral density and osteoarthritis: data from the Baltimore Longitudinal Study of Aging. Osteoarthr Cartil. 2004;12:45–8.Google Scholar
  14. 14.
    El Miedany YM, Mehanna AN, et al. Altered bone mineral metabolism in patients with osteoarthritis. Joint Bone Spine. 2000;67(6):521–7.PubMedGoogle Scholar
  15. 15.
    Perry ME, et al. Relationships between self-reported osteoarthritis (OA), bone mineral density (BMD) and radiographic scores using dual energy X-ray absorptiometry (DXA). Scott Med J. 2015;60(3):25–33.Google Scholar
  16. 16.
    Hannan MT, Andersin JJ, et al. Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study. Arthritis Rheum. 1993;36(12):1671–80.PubMedGoogle Scholar
  17. 17.
    Demirağ MD, Özkan S, et al. Associations between obesity and the radiographic phenotype in knee osteoarthritis. Turk J Med Sci. 2017;47(2):424–9.PubMedGoogle Scholar
  18. 18.
    Crowninshield RD, Rosenberg AG, et al. Changing demographics of patients with total joint replacement. Clin Orthop Relat Res. 2006;443:266–72.PubMedGoogle Scholar
  19. 19.
    Arden NK, Griffiths GO, et al. The association between osteoarthritis and osteoporotic fracture: the Chingford Study. Br J Rheumatol. 1996;35:1299–304.PubMedGoogle Scholar
  20. 20.
    Arden NK, Crozier S, et al. Knee pain, knee osteoarthritis, and the risk of fracture. Arthritis Rheum. 2006;55(4):610–5.PubMedGoogle Scholar
  21. 21.
    Bergink AP, Van Der Klift M, et al. Osteoarthritis of the knee is associated with vertebral and nonvertebral fractures in the elderly: the Rotterdam Study. Arthritis Care Res. 2003;49:648–57.Google Scholar
  22. 22.
    Chan MY, Center JR, et al. Bone mineral density and association of osteoarthritis with fracture risk. Osteoarthr Cartil. 2014;22(9):1251–8.PubMedGoogle Scholar
  23. 23.
    Jones G, Nguyen T, et al. Osteoarthritis, bone density, postural stability, and osteoporotic fractures: a population based study. J Rheumatol. 1995;22(5):921–5.PubMedGoogle Scholar
  24. 24.
    Lee S, Kim TN, et al. Knee osteoarthritis is associated with increased prevalence of vertebral fractures despite high systemic bone mineral density: a cross-sectional study in an Asian population. Mod Rheumatol. 2014;24(1):174–81.Google Scholar
  25. 25.
    Birch C, Hunter D, et al. Development of a novel imaging process to determine the clinical applicability of bone mineral density assessment of the osteoarthritic knee: a research proposal. Work Pap Health Sci. 2014;1(9):1–7.Google Scholar
  26. 26.
    Liu G, Peacock M, et al. Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women. Osteoporos Int. 1997;7(6):564–9.PubMedGoogle Scholar
  27. 27.
    Ding M, Odgaard A, et al. Changes in the three-dimensional microstructure of human tibial cancellous bone in early osteoarthritis. J Bone Joint Surg Br Vol. 2003;85(6):906–12.Google Scholar
  28. 28.
    Mansell JP, Bailey AJ. Abnormal cancellous bone collagen metabolism in osteoarthritis. J Clin Investig. 1998;101(8):1596–603.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Legrand E, Chappard D, et al. Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res. 2000;15(1):13–9.PubMedGoogle Scholar
  30. 30.
    Manninen P, Riihimäki H, et al. Overweigh gender and knee osteoarthritis. Int J Obes. 1996;20(6):595–7.Google Scholar
  31. 31.
    Yang S, Shen X. Association and relative importance of multiple obesity measures with bone mineral density: the national health and nutrition examination survey 2005–2006. Arch Osteoporos. 2015;10:14.PubMedGoogle Scholar
  32. 32.
    Papakitsou EF, Margioris AN, et al. Body mass index (BMI) and parameters of bone formation and resorption in postmenopausal women. Maturitas. 2004;47(3):185–93.PubMedGoogle Scholar
  33. 33.
    Walsh JS, Vilaca T. Obesity, type 2 diabetes and bone in adults. Calcif Tissue Int. 2017;100(5):528–35.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Saito M, Kida Y, et al. Diabetes, collagen and bone quality. Curr Osteoporos Rep. 2014;12(2):181–8.PubMedGoogle Scholar
  35. 35.
    McNerny EMB, Nikolas TL. Bone quality in chronic kidney disease: definitions and diagnostics. Curr Osteoporos Rep. 2017;15(3):207–13.PubMedGoogle Scholar
  36. 36.
    Vestergaard P, Rejnmark L, et al. Osteoarthritis and risk of fractures. Calcif Tissue Int. 2009;84(4):249–56.PubMedGoogle Scholar
  37. 37.
    Cumming RG, Klineberg RJ. Epidemiological study of the relation between arthritis of the hip and hip fractures. Ann Rheum Dis. 1993;52:707–10.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Arden NK, Nevitt MC, et al. Osteoarthritis and risk of falls, rates of bone loss, and osteoporotic fractures. Arthritis Rheum. 1999;42(7):1378–85.PubMedGoogle Scholar
  39. 39.
    Jones G, Nquyen T, et al. A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly. J Rheumatol. 1995;22(5):932–6.PubMedGoogle Scholar
  40. 40.
    Vennu V, Bindawas SM. Relationship between falls, knee osteoarthritis, and health-related quality of life: data from the Osteoarthritis Initiative study. J Clin Interv Aging. 2014;9:793–800.Google Scholar
  41. 41.
    Doré AL, Golightly YM, et al. Lower-extremity osteoarthritis and the risk of falls in a community-based longitudinal study of adults with and without osteoarthritis. Arthritis Care Res. 2015;67(5):633–9.Google Scholar
  42. 42.
    Lalmohamed A, Opdam F, et al. Knee arthroplasty and risk of hip fracture: a population-based, case–control study. Calcif Tissue Int. 2012;90(2):144–50.PubMedGoogle Scholar
  43. 43.
    Prieto-Alhambra D, Javaid MK, et al. Changes in hip fracture rate before and after total knee replacement due to osteoarthritis: a population-based cohort study. Ann Rheum Dis. 2011;70(1):134–8.PubMedGoogle Scholar
  44. 44.
    Bousson V, Bergot C, et al. Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. Osteoporos Int. 2012;23(5):1489–501.PubMedGoogle Scholar
  45. 45.
    Hopkins SJ, Toms AD, et al. A study investigating short- and medium-term effects on function, bone mineral density and lean tissue mass post-total knee replacement in a Caucasian female post-menopausal population: implications for hip fracture risk. Osteoporos Int. 2016;27(8):2567–76.PubMedGoogle Scholar
  46. 46.
    Hopkins SJ, Smith CW, et al. Relationship between spine bone mineral density and trabecular bone score in postmenopausal populations following total knee replacement or leg fracture. Osteoporos Int. 2012;23:S582.Google Scholar
  47. 47.
    Legrand E, Chappard D, et al. Bone mineral density and vertebral fractures in men. Osteoporos Int. 1999;10:265–70.PubMedGoogle Scholar
  48. 48.
    Marshall D, Johnell O, et al. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J. 1996;312(7041):1254–9.Google Scholar
  49. 49.
    De Laet CE, Van Hout BA, et al. Bone density and risk of hip fracture in men and women: cross sectional analysis. Br Med J. 1997;315(7102):221–5.Google Scholar
  50. 50.
    Cummings SR, Black DM, et al. Bone density at various sites for prediction of hip fractures. Lancet. 1993;341(8837):72–5.PubMedGoogle Scholar
  51. 51.
    Cummings SR, Nevitt MC, et al. Risk factor for hip fracture in white women. N Engl J Med. 1995;332(12):767–74.PubMedGoogle Scholar
  52. 52.
    Melton LJ 3rd, Wahner HW, et al. Osteoporosis and the risk of hip fracture. Am J Epidemiol. 1986;124(2):254–61.PubMedGoogle Scholar
  53. 53.
    Beaupre LA, Rezansoff A, et al. Bone mineral density changes in the hip and spine of men and women 1-year after primary cemented total knee arthroplasty: prospective cohort study. J Arthroplast. 2015;30(15):2185–9.Google Scholar
  54. 54.
    Gazdzik TS, Gajda T, et al. Bone mineral density changes after total knee arthroplasty: one-year follow-up. J Clin Densitom. 2008;11(3):345–50.PubMedGoogle Scholar
  55. 55.
    Ishii Y, Yagisawa K, et al. Changes in bone mineral density of the proximal femur after total knee arthroplasty. J Arthroplast. 2000;15(4):519–22.Google Scholar
  56. 56.
    Kim KK, Won YY, et al. Changes in bone mineral density of both proximal femurs after total knee arthroplasty. Clin Orthop Surg. 2014;6(1):43–8.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Li MG, Nilsson KG. Changes in bone mineral density at the proximal tibia after total knee arthroplasty: a 2-year follow-up of 28 knees using dual energy X-ray absorptiometry. J Orthop Res. 2000;18(1):40–7.PubMedGoogle Scholar
  58. 58.
    Liu TK, Yang RS, et al. Periprosthetic bone mineral density of the distal femur after total knee arthroplasty. Int Orthop. 1995;19(6):346–51.PubMedGoogle Scholar
  59. 59.
    Petersen MM, Nielsen PT, et al. Changes in bone mineral density of the proximal tibia after uncemented total knee arthroplasty. A 3-year follow-up of 25 knees. Acta Orthop Scand. 1995;66(6):513–6.PubMedGoogle Scholar
  60. 60.
    Soininvaara TA, Miettinen HJ, et al. Bone mineral density in the proximal femur and contralateral knee after total knee arthroplasty. J Clin Densitom. 2004;7(4):424–31.PubMedGoogle Scholar
  61. 61.
    Soininvaara TA, Miettinen HJ, et al. Periprosthetic tibial bone mineral density changes after total knee arthroplasty: one-year follow-up study of 69 patients. Acta Orthop Scand. 2004;75(5):600–5.PubMedGoogle Scholar
  62. 62.
    Mau-Moeller A, Behrens M, et al. Modulation and predictors of periprosthetic bone mineral density following total knee arthroplasty. Biomed Res Int. 2015;2015:418168.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Järvenpää J, Soininvaara TA, et al. Changes in bone mineral density of the distal femur after total knee arthroplasty: a 7-year DEXA follow-up comparing results between obese and nonobese patients. Knee J. 2014;21(1):232–5.Google Scholar
  64. 64.
    Mintzer CM, Robertson DD, et al. Bone loss in the distal anterior femur after total knee arthroplasty. Clin Orthop Relat Res. 1990;260:135–43.Google Scholar
  65. 65.
    Jaroma A, Soininvaara TA, et al. Periprosthetic tibial bone mineral density changes after total knee arthroplasty a 7-year follow-up of 86 patients. Acta Orthop. 2016;87(3):268–73.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Lavernia CJ, Rodriguez JA, et al. Bone mineral density of the femur in autopsy retrieved total knee arthroplasties. J Arthroplast. 2014;29(8):1681–6.Google Scholar
  67. 67.
    Lonner JH, Klotz M, et al. Changes in bone density after cemented total knee arthroplasty: influence of stem design. J Arthroplast. 2001;16(1):107–11.Google Scholar
  68. 68.
    Im GI, Kwon OJ, et al. The relationship between osteoarthritis of the knee and bone mineral density of proximal femur: a cross-sectional study from a Korean population in women. Clin Orthop Surg. 2014;6(4):420–5.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Karbowski A, Schwitalle M, et al. Periprosthetic bone remodelling after total knee arthroplasty: early assessment by dual energy X-ray absorptiometry. Arch Orthop Trauma Surg. 1999;119(5–6):324–6.PubMedGoogle Scholar
  70. 70.
    Levitz CL, Lotke PA, et al. Long-term changes in bone mineral density following total knee replacement. Clin Orthop Relat Res. 1995;321:68–72.Google Scholar
  71. 71.
    Van Loon CJ, Oyen WJ, et al. Distal femoral bone mineral density after total knee arthroplasty: a comparison with general bone mineral density. Arch Orthop Trauma Surg. 2001;121(5):282–5.PubMedGoogle Scholar
  72. 72.
    Hahn MH, Won YY. Bone mineral density changes after total knee replacement in women over the age of 65. J Bone Metab. 2013;20(2):105–9.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Petersen MM, Gehrchen PM, et al. Effect of hydroxyapatite-coated tibial components on changes in bone mineral density of the proximal tibia after uncemented total knee arthroplasty: a prospective randomized study using dual-energy x-ray absorptiometry. J Arthroplast. 2005;20(4):516–20.Google Scholar
  74. 74.
    Mann T, Eisler T, et al. Larger femoral periprosthetic bone mineral density decrease following total hip arthroplasty for femoral neck fracture than for osteoarthritis: a prospective, observational cohort study. J Orthop Res. 2015;33(4):504–12.PubMedGoogle Scholar
  75. 75.
    Cameron HU, Cameron G. Stress-relief osteoporosis of the anterior femoral condyles in total knee replacement: a study of 185 patients. Orthop Rev. 1987;16(7):449–56.PubMedGoogle Scholar
  76. 76.
    Van Lenthe GH, de Waal Malefijt MC, et al. Stress shielding after total knee replacement may cause bone resorption in the distal femur. J Bone Joint Surg Br Vol. 1997;79(1):117–22.Google Scholar
  77. 77.
    Hopkins SJ, Smith CW, et al. A study investigating the long-term effects on function, bone mineral density and lean tissue mass post total knee replacement in a female postmenopausal population. Osteoporos Int. 2012;23:S552.Google Scholar
  78. 78.
    Meek RM, Norwood T, et al. The risk of peri-prosthetic fracture after primary and revision total hip and knee replacement. Bone Joint J. 2011;93(1):96–101.Google Scholar
  79. 79.
    Toogood PA, Vail TP. Periprosthetic fractures: a common problem with a disproportionately high impact on healthcare resources. J Arthroplast. 2015;30(10):1688–91.Google Scholar
  80. 80.
    Vala CH, Kärrholm J, et al. OC12 Risk for hip fracture ten years before and after total knee replacement surgery in the entire Swedish population. Abstract book: WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, 14–17 April 2016, Malaga, Spain Osteoporosis International, 27(Supplement 1) 2016. http://2016.wco-iof-esceo.org/sites/all/files/wco16/WCO16-AbstractBook.pdf. Accessed 23 March 2017.
  81. 81.
    Cordeiro EN, Costa RC, et al. Periprosthetic fractures in patients with total knee arthroplasties. Clin Orthop Relat Res. 1990;252:182–9.Google Scholar
  82. 82.
    Dennis DA. Periprosthetic fractures following total knee arthroplasty. J Bone Joint Surg (Am Vol). 2001;83(1):120–30.Google Scholar
  83. 83.
    Merkel KD, Johnson EW Jr. Supracondylar fracture of the femur after total knee arthroplasty. J Bone Joint Surg (Am Vol). 1986;68(1):29–43.Google Scholar
  84. 84.
    Engh GA, Ammeen DJ, et al. Instructional course lectures, the american academy of orthopaedic surgeons—periprosthetic fractures adjacent to total knee implants. Treatment and clinical results. J Bone Joint Surg (Am Vol). 1997;79:1100–13.Google Scholar
  85. 85.
    Beals RK, Tower SS. Periprosthetic fractures of the femur. An analysis of 93 fractures. Clin Orthop Relat Res. 1996;327:238–46.Google Scholar
  86. 86.
    Matsumoto H, Okuno M, et al. Incidence and risk factors for falling in patients after total knee arthroplasty compared to healthy elderly individuals. Yonago Acta Medica. 2014;57(4):137–45.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Soison A, Riratanapong S, et al. Prevalence of fall in patients with total knee arthroplasty living in the community. J Med Assoc Thail. 2014;97(12):1338–43.Google Scholar
  88. 88.
    Ikutomo H, Nagai K, et al. Falls in patients after total hip arthroplasty in Japan. J Orthop Sci. 2015;20(4):663–8.PubMedGoogle Scholar
  89. 89.
    Swinkels A, Allain TJ. Physical performance tests, self-reported outcomes, and accidental falls before and after total knee arthroplasty: an exploratory study. Physiother Theory Pract. 2013;29(6):432–42.PubMedGoogle Scholar
  90. 90.
    Swinkels A, Newman JH, et al. A prospective observational study of falling before and after knee replacement surgery. Age Ageing. 2009;38(2):175–81.PubMedGoogle Scholar
  91. 91.
    Carulli C, Civinini R, et al. The use of anti-osteoporosis drugs in total knee arthroplasty. Aging Clin Exp Res. 2011;23(2):38–9.PubMedGoogle Scholar
  92. 92.
    Prieto-Alhambra D, Javaid MK, et al. Bisphosphonate use and risk of post-operative fracture among patients undergoing a total knee replacement for knee osteoarthritis: a propensity score analysis. Osteoporos Int. 2011;22(5):1555–71.PubMedGoogle Scholar
  93. 93.
    Teng S, Yi C, et al. Bisphosphonate use and risk of implant revision after total hip/knee arthroplasty: a meta-analysis of observational studies. Public Libr Sci. 2015;10(10):e0139927.Google Scholar
  94. 94.
    Ma S, Goh EL. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci Rep. 2017;7:43399.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Kharwadkar N, Mayne B, et al. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res. 2017;6(3):144–53.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Bjarnason NH, Hassager C, et al. Postmenopausal bone remodelling and hormone replacement. Clim J Int Menopause Soc. 1998;1(1):72–9.Google Scholar
  97. 97.
    Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. J Am Med Assoc. 2001;285(22):2891–7.Google Scholar
  98. 98.
    Lufkin EG, Wahner HW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992;117(1):1–9.PubMedGoogle Scholar
  99. 99.
    Beral V, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet. 2003;362(9382):419–27.PubMedGoogle Scholar
  100. 100.
    Jordan N, Barry M, et al. Comparative effects of antiresorptive agents on bone mineral density and bone turnover in postmenopausal women. Clin Interv Aging. 2006;1(4):377–87.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Ettinger B, Black DM, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. J Am Med Assoc. 1999;282(7):637–45.Google Scholar
  102. 102.
    Romero A, Alonso C, et al. Risk of venous thromboembolic disease in women a qualitative systematic review. Eur J Obstet Gynecol Reprod Biol. 2005;121(1):8–17.PubMedGoogle Scholar
  103. 103.
    Cosman F, Baz-Hecht M, et al. Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature. Thromb Res. 2005;116(1):1–13.PubMedGoogle Scholar
  104. 104.
    Arnett T. Basics of bone biology. Osteoporos Rev. 2015;23(2):12–6.Google Scholar
  105. 105.
    National Osteoporosis Society. Drug treatments for osteoporosis. 2016. https://nos.org.uk/media/1594/drug-treatments-for-osteoporosis-parathyroid-hormone-treatment-january-2016.pdf. Accessed 23 March 2017.
  106. 106.
    Borba VZC, Manas NCP. The use of PTH in the treatment of osteoporosis. Arq Bras Endocrinol Metabol. 2010;54(2):213–9.PubMedGoogle Scholar
  107. 107.
    Almeida MM, Nani EP, et al. Strontium ranelate increases osteoblast activity. Tissue Cell. 2016;48(3):183–8.PubMedGoogle Scholar
  108. 108.
    National Osteoporosis Society. National osteoporosis update. Osteoporos Rev. 2017;25(1):14.Google Scholar
  109. 109.
    Abrahamsen B, Grove EL, et al. Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate. Osteoporos Int. 2014;25(2):757–62.PubMedGoogle Scholar
  110. 110.
    Minoda Y, Ikebuchi M, et al. A cemented mobile-bearing total knee replacement prevents periprosthetic loss of bone mineral density around the femoral component: a matched cohort study. J Bone Joint Surg Br Vol. 2010;92(6):794–8.Google Scholar
  111. 111.
    Zhang QH, Cossey A, et al. Stress shielding in periprosthetic bone following a total knee replacement: effects of implant material, design and alignment. Med Eng Phys. 2016;38(12):1481–8.PubMedGoogle Scholar
  112. 112.
    Howard JL, Kudera LE, et al. Early results of the use of tantalum femoral cones for revision total knee arthroplasty. J Bone Joint Surg Am. 2011;93(5):478–84.PubMedGoogle Scholar
  113. 113.
    Lachiewicz B, Handerson RA, et al. Can tantalum cones provide fixation in complex revision knee arthroplasty? Clin Orthop Relat Res. 2012;470(1):199–204.PubMedGoogle Scholar
  114. 114.
    Harrison AK, Gioe TJ, et al. Do porous tantalum implants help preserve bone?: Evaluation of tibial bone density surrounding tantalum tibial implants in TKA. Clin Orthop Relat Res. 2010;468(10):2739–45.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Winther N, Jensen C, et al. Changes in bone mineral density of the proximal tibia after uncemented total knee arthroplasty. A prospective randomized study. Int Orthop. 2016;40(2):285–94.PubMedGoogle Scholar
  116. 116.
    Minoda Y, Kobayashi A, et al. Porous tantalum tibial component prevents periprosthetic loss of bone mineral density after total knee arthroplasty for five years-a matched cohort study. J Arthroplast. 2013;28(10):1760–4.Google Scholar
  117. 117.
    Jensen CL, Petersen MM, et al. Bone mineral density changes of the proximal tibia after revision total knee arthroplasty. A randomised study with the use of porous tantalum metaphyseal cones. Int Orthop. 2012;36(9):1857–63.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Faizan A, Bhowmik-Stoker M, et al. Development and verification of novel porous titanium metaphyseal cones for revision total knee arthroplasty. J Arthroplast. 2017;32(6):1946–53.Google Scholar
  119. 119.
    Family R, Solati-Hashjin M, et al. Surface modification for titanium implants by hydroxyapatite nanocomposite. Caspian J Intern Med. 2012;3(3):460–5.PubMedPubMedCentralGoogle Scholar
  120. 120.
    Cook SD, Thomas KA, et al. Hydroxyapatite-coated for orthopaedic implant applications. Clin Orthop Relat Res. 1988;232:225–43.Google Scholar
  121. 121.
    Bøe BG, Støen RØ, et al. Coating of titanium with hydroxyapatite leads to decreased bone formation. Bone Joint Res. 2012;1(6):125–30.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Watters TS, Martin JR, et al. Porous-coated metaphyseal sleeves for severe femoral and tibial bone loss in revision TKA. J Arthroplast. 2017;S0883-5403(17):30536–3.Google Scholar
  123. 123.
    Dalury DF, Barrett WP. The use of metaphyseal sleeves in revision total knee arthroplasty. Knee. 2016;23(3):545–8.PubMedGoogle Scholar
  124. 124.
    Maier GS, Kolbow K, et al. The importance of bone mineral density in hip arthroplasty: results of a survey asking orthopaedic surgeons about their opinions and attitudes concerning osteoporosis and hip arthroplasty. Adv Orthop. 2016;2016:8079354.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Di Gregorio S, Del Rio L, et al. Comparison between different bone treatments on areal bone mineral density (aBMD) and bone microarchitectural texture as assessed by the trabecular bone score (TBS). Bone J. 2015;75:138–43.Google Scholar
  126. 126.
    Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359(9321):1929–36.PubMedGoogle Scholar
  127. 127.
    Ferket BS, Feldman Z, et al. Impact of total knee replacement practice: cost effectiveness analysis of data from the osteoarthritis initiative. Br Med J. 2017;356:j1131.Google Scholar
  128. 128.
    Skou ST, Roos EM, et al. A randomized controlled trial of total knee replacement. New J Med. 2015;373:1597–606.Google Scholar
  129. 129.
    Robertsson O, Dunbar M, et al. Patient satisfaction after knee arthroplasty: a report on 27,372 knees operated on between 1981 and 1995 in Sweden. Acta Orthop Scand. 2000;71(3):262–7.PubMedGoogle Scholar

Copyright information

© The Author(s) 2017

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.University of Exeter Medical SchoolExeterUK

Personalised recommendations