Disease Management & Health Outcomes

, Volume 12, Issue 6, pp 409–418

The Burden of Osteoporosis and the Case for Disease Management

Authors

    • Department of Clinical BiochemistryRoyal Liverpool University Hospital
Review Article

DOI: 10.2165/00115677-200412060-00008

Cite this article as:
Fraser, W.D. Dis-Manage-Health-Outcomes (2004) 12: 409. doi:10.2165/00115677-200412060-00008
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Abstract

Currently, osteoporosis, defined as low bone mineral density (BMD), affects 30% of postmenopausal women and 8% of men >50 years old in Western society and these percentages are likely to increase as our elderly population expands. Osteoporosis-related fractures increase with age and reductions in BMD, with the greatest increase in hip, followed by vertebral, and then wrist fractures. Osteoporosis is associated with significant mortality and for each 1 SD decrease in BMD there is a 1.5-fold increase in mortality risk. Following a hip fracture, 25–30% of patients will die within 3–6 months and in some populations hip fractures account for 1.5% of all deaths. Osteoporosis and related fractures are associated with significant morbidity, with loss of independence, psychological effects, and an overall decreased quality of life.

The current financial cost of osteoporosis in the US is $US14 billion and in the UK just over £1 billion, and these costs will increase 3- to 8-fold over the next 50 years. Treatments are available that have been shown to significantly increase BMD, decrease bone turnover, and as a result decrease fracture incidence. For reductions in both vertebral and fracture, the evidence is strongest for the use of the bisphosphonates alendronate and risedronate; while for vertebral fracture, effective treatments include raloxifene, etidronate, calcitonin, and calcium plus vitamin D. Recent data suggest that hormone replacement therapy (HRT) can prevent hip and vertebral fractures, but long-term use, or commencement in elderly women of some continuous combined preparations, is no longer recommended.

It has been recognized that bone turnover and bone quality contribute to fracture risk and, therefore, biochemical assessment of bone resorption and formation may increase the clinical and cost effectiveness of treatment. Using a conservative estimate of fracture reduction (35%) over a 5-year period, an intervention costing $US500 (£333) per year is cost effective when targeted to women with osteoporosis who are ≥65 years of age. It has been calculated that the lower the intervention cost and the higher the effectiveness of treatment the lower the age at which the treatment would be cost effective. The increasing healthcare burden and effective treatments make osteoporosis an excellent candidate for disease management programs.

Osteoporosis is a systemic disease that leads to an increased risk of fractures as a result of a reduction in bone mass and quality.[1,2] Using the WHO definition of osteoporosis, based on bone mineral density (BMD) measurement taken at any bodily site (table I), in the US, 30% of postmenopausal women of all ages and 8% of the male population >50 years old being classified as having osteoporosis.[3,4] The presence of a fragility or minimal trauma fracture (fracture occurring after a fall from a chair or standing) and low bone density (T score ≤2.5) is classified as severe osteoporosis. While BMD is a major contributor to risk, other factors, including age, body mass index, falls, bone quality, and the rate at which bone is being resorbed by osteoclasts and formed by osteoblasts, play an important part in determining whether a patient will experience a fracture.[5,6]
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Table I

WHO definitions of bone mineral density (BMD)

1. Burden of Disease and Impact of Osteoporosis

The prevalence of osteoporosis has been calculated using the US National Center for Health Statistics’ National Health and Nutrition Examination Survey (NHANES) database and there is a clear association with increasing age.[7] Using hip BMD, 20% of postmenopausal women in the US aged 65–69 years has osteoporosis and this increases to just over 50% in those aged ≥80 years.[7] Fracture incidence increases with age, with the greatest increase of fractures observed at hip, followed by vertebral, then wrist sites.[8] This pattern of osteoporosis-related fractures appears to be consistent throughout the Western world and a 2-fold increase in fracture risk is observed for each 1 SD reduction in BMD of the hip and spine.[9] Hip fractures are much more common in Caucasians than in other ethnic groups and the variation in fracture rates in populations may reflect racial differences.

Osteoporosis is associated with increased mortality and for each 1 SD that BMD is decreased the mortality risk is increased 1.5-fold.[1012] One in three women and one in five men will experience a hip fracture by the age of 80 years and, following a hip fracture, between 20% and 30% of patients will die within 3–6 months of the fracture.[1315] In a study of 160 000 hip fractures in Swedish men and women aged >50 years, it was calculated that causally-related deaths (directly or indirectly) to hip fractures comprised 17–32% of all deaths and accounted for >1.5% of all deaths in this population.[16] Interestingly, the risk of death was greater for men than women. Excess mortality is associated with hip fracture and vertebral fracture;[1722] however, this may be secondary to other medical conditions and general health that may be unrelated to osteoporosis.

Data have accumulated that demonstrate the importance of preventing fractures and recognizing the existence of a fracture. Vertebral fractures are associated with increased risk of further vertebral fracture, resulting in height loss and kyphosis and an increased risk of non-vertebral fractures independent of BMD.[2326] A prospective study has confirmed that the greatest risk for fracture exists during the time immediately following the initial fracture.[27] In another study, a 5-fold increase in the risk of fracture was observed in patients with previous fracture at baseline compared with those without fracture and the incidence of new vertebral fracture in patients who developed an incident fracture was 19.2% (95% CI 13.6%, 24.8%).[28] It is, therefore, essential that treatments demonstrate efficacy in preventing further fracture in the first year following a new fracture.

Many women who have a low BMD may never manifest any signs of osteoporosis or experience a fracture. However, the very knowledge that they have a low BMD can significantly affect these women, because a fear of future fractures may cause them to make subsequent alterations to their daily life to prevent falls and fractures. A study of French women with osteoporosis has shown a negative effect of osteoporosis on quality of life (QOL) even in the absence of known fractures.[29] Lower QOL scores were noted with decreasing BMD. Height loss and kyphosis were significantly associated with difficulty in daily activities, alteration of daily routines, and a fear of experiencing future fractures. The negative impact of osteoporosis on QOL was related more to the physical manifestations than to BMD alone. Other psychological effects have been reported in women with osteoporosis, such as stress, sadness, anger, and denial.[30]

2. Costs of Osteoporosis

The total cost of osteoporosis in the US has been estimated at $US14 billion per year (1996–1997 values).[31] These costs are predicted to increase 3- to 8-fold over a 50-year period as the elderly population in the US expands, particularly those aged >85 years.[32]

Although the social and acute care costs of osteoporotic fractures in the UK have been quantified at £1.03 billion per annum (1998–1999 values),[33,34] significantly greater costs are liable to accrue in terms of the long-term outcome of this condition. Population statistics have been used to estimate the growth in the number of elderly individuals in the population over the next decade. Assuming that the distribution of BMD in the population remains constant and the fracture rates for the population remain the same, the costs for treating osteoporosis-related fractures in the UK would increase to £2.1 billion per year by 2010.[35]

Total hospital costs for vertebral fractures in EU countries have been estimated using national data sets at €377 million per year and the average cost of a vertebral fracture was 63% of that of a hip fracture (2001 values).[36] In the US, non-hip fracture costs account for 37% of healthcare spending and 9% of this expenditure is on outpatient care.[37]

The additional costs to society and the individual from osteoporosis-related fractures are more difficult to quantify. Significant loss of independence has been documented following hip fracture[38] and the requirement for a carer or entry into a nursing home is high, with over 140 000 admissions in the US annually accounting for 28% of the osteoporosis-related healthcare costs.[39] In the UK, it has been predicted that 10% of all patients with hip fractures will end up in nursing home care and that it is likely they will remain there for the remainder of their lives.[35] Loss of the ability to live independently in the community has a significant detrimental effect on QOL. Eighty percent of elderly women (>75 years of age) in a recent survey stated they would rather be dead than experience the loss of independence and deterioration in QOL that results from a bad hip fracture.[40]

2.1 Cost of Bone Mineral Density Measurements

The costs of BMD measurement for the UK population have been estimated based on a requirement for 902 BMD scans annually per 100 000 population. At an average cost of £48 per scan, the provision of these investigations for an average health district of 300 000 would cost £129 888 (2001–2002 values).[41]

Clearly, if osteoporosis is not to become a major burden on society in the future, it is essential that an appropriate medical strategy be established to prevent the development of osteoporosis and to treat established osteoporosis when it is detected.

3. Secondary Causes of Osteoporosis

A thorough diagnostic workup of patients with osteoporosis is required to ensure a causal approach to therapy that will yield optimal outcomes in terms of increasing bone mass and reducing fractures. At presentation it is essential to rule out secondary causes of osteoporosis, including serious diseases such as malignancy.[42,43] This evaluation requires radiological, biochemical, and hematological investigation of the patient prior to initiation of therapy for osteoporosis. Exclusion of serious secondary causes of osteoporosis (table II) is an essential step in the process of managing patients with osteoporosis. Although the diagnosis may be evident on clinical examination, the question of excluding disease by additional formal testing has been a matter for debate.[44] As a minimum the biochemical, hematological, and radiological tests in table III should be performed and additional tests should be considered where there is a high index of clinical suspicion, where risk factors and severity of disease suggest a pathological cause,[45] or where abnormalities have been revealed on initial investigations. By adopting this approach during the initial evaluation of patients, it should be possible to avoid inappropriate and ineffective prescriptions of the available expensive treatments. The performance of each of these tests has an associated cost and the workup outlined in table III will average £42 in the UK ($US62) per patient (2003 values) [personal observation]. These costs may be higher depending on availability and local laboratory practice.
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Table II

Secondary causes of osteoporosis

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Table III

Diagnostic tests for secondary causes of osteoporosis

4. Measuring the Effectiveness of Treatment

The effectiveness of treatment can be assessed by estimating the reduction of clinically significant fractures; however, the actual fracture incidence can be underestimated, and so this method is rarely used in clinical trials.[46] Although the ability to accurately assess treatment outcomes is improved when radiologically proven fractures are considered, there is still a debate about what constitutes a fracture.[4749] An additional way of assessing the effectiveness of treatments is the use of BMD, where a consistent relationship exists between BMD and fracture.[14] When the relationship between BMD and fracture is analyzed in terms of treatment effect using regression analysis it is found to be helpful mainly in predicting the impact of treatment on vertebral but not non-vertebral fracture.[46] However, some studies have shown that there is a significant effect on fracture incidence even when there is little or no significant increase in BMD[3,5052], and so there may be additional factor(s) playing a role in the genesis of fracture. Another method of determining the efficacy of any treatment is to measure changes in the biochemical estimates of bone turnover, which can predict the changes in bone mass that will occur and the likelihood of a fracture.[53,54] It has been shown that the rate of bone turnover and a patient’s response to treatment is an important predictor of efficacy.[55]

5. Therapeutic Intervention

It is clear that the nature of osteoporosis would lend itself to a public health approach to primary prevention. An alteration of environmental factors, diet, and exercise, a reduction of excessive alcohol consumption, and cessation of smoking could all contribute to an improvement in BMD and reduction in fracture risk. Unfortunately, each of these factors in isolation has a small or poorly quantified effect and no population-level intervention has been implemented related to osteoporosis. The provision of milk to adolescent children can have a significant effect on BMD and bone mineral content;[56] interestingly, the UK government stopped providing milk free of charge to all children attending state schools.

Greater attempts should be made to reduce the risk of falling for elderly people. In many cases, if an individual avoids a fall then they will not experience a fracture. Home assessment may be helpful to identify dangers in the immediate environment such as loose-fitting carpets and rugs, ill-fitting shoes and slippers, poor lighting, inappropriate storage of household utensils, and structural risks such as loose banisters. General health measures including the provision of glasses and hearing aids and the avoidance of sedatives will be helpful.

An evidence base that is strong enough to conclude that several pharmacological interventions can be effective in reducing fractures has been produced in recent years. Several treatments have been shown to reduce vertebral fractures and a recent meta-analysis of the data has pulled together the important evidence and has provided important conclusions.[46,5764]

5.1 Prevention of Osteoporosis

5.1.1 Hormone Replacement Therapy and Prevention

Much of the data on prevention of fractures in postmenopausal women focus on the use of hormone replacement therapy (HRT). Observational studies clearly indicate that there is an association between HRT use and fracture reduction,[6567] and recent meta-analyses have concluded that HRT results in a significant reduction in fractures.[68,69] A large prospective study of postmenopausal women in Scotland concluded that women using HRT immediately after menopause had substantial reductions in all fractures.[70] This study also concluded that HRT was more cost effective over a 6-year period of use, in terms of cost per fracture averted, in high-risk populations. The results were in agreement with a previous study that concluded that HRT, given on the basis of screening an asymptomatic population, was less cost effective than targeting higher risk groups.[71] The use of HRT in this group of women results in a 50% reduction in appendicular fractures at a cost benefit of £11 000 per high-risk and £2000 per low-risk fracture averted.

The use of HRT for the prevention of chronic diseases has recently been questioned following the publication of two important studies. The Women’s Health Initiative (WHI) study[72] and the Million Women Study[73] have both provided data regarding the risks associated with the long-term use of HRT. A significant increase in breast cancer risk was reported in both studies and the Million Women Study suggested that continuous combined HRT (containing both estrogen and progesterone) was associated with the highest incidence of breast cancer. Cardiovascular-associated mortality, cerebrovascular accidents, and thromboembolic events were all increased in the WHI study. Calculations of the cost effectiveness and benefits of HRT now need to take into account the impact of these deleterious effects.

5.2 Treatment of Osteoporosis

5.2.1 Vertebral Fractures

Vitamin D (in combination with calcium), calcitonin, raloxifene, and the bisphosphonates etidronate, risedronate, and alendronate all significantly reduce vertebral fractures. This inference is made on the basis of the methodology, quality, magnitude of effect, confidence intervals, and consistency of study results. A large number of studies were analyzed for each intervention and reported in individual meta-analyses including calcium,[63] vitamin D,[64] calcitonin,[62] raloxifene,[60] HRT,[61] etidronate,[46] risedronate,[59] and alendronate.[58]

HRT in the meta-analysis[61] did not have a significant effect on vertebral fractures because the pooled estimate from the randomized trials had a wide confidence interval. However, the analysis excluded the recent WHI study that enrolled over 16 000 women in the US and detected a significant effect on vertebral-fracture incidence in those who received a continuous combined HRT preparation.[72] Reductions in the magnitude of vertebral fracture as a result of changes in bone turnover and BMD provide additional support for the effect of HRT on vertebral fracture.[68,69]

Raloxifene was the first selective estrogen receptor modulator to be approved for use in the prevention and treatment of postmenopausal osteoporosis. Although only a modest increase in both femoral neck and lumbar spine BMD (2–3%) was observed in patients treated with raloxifene 60mg daily for 24–36 months,[74] this resulted in a significant reduction in vertebral fracture rates (38–52%). However, there was no significant reduction in hip fracture in the three groups (placebo, roloxifene 60mg/day, and raloxifene 120mg/day) when compared with control patients receiving calcium and vitamin D.[75] An additional beneficial effect of raloxifene was the 76% reduction in breast cancer incidence (mainly estrogen receptor positive) observed in women in these trials.[76] The main adverse effects were muscle cramps and increased flushing, but a more serious effect was a modest increase in the venous thrombosis risk (similar to the thrombosis risk observed with HRT). Obviously, a cost-effective analysis of raloxifene should take into account any additional benefit observed through a reduction in the incidence of breast cancer; however, this reduction needs to be confirmed by further studies.

5.2.2 Non-Vertebral Fractures

Only alendronate and risedronate have shown convincing evidence for reducing non-vertebral fractures.[58,59] There are minimal trial data and epidemiological evidence for all other treatments and comparators, with the confidence interval overlapping the effect for the comparison of the studies.[46,6064]

It is possible that some treatments are more effective in subpopulations of patients and that the magnitude of effect is greater in those patients. The evidence for an effect of calcium plus vitamin D in patients who are vitamin D deficient, which may result in secondary hyperparathyroidism, is much stronger than the effect in the overall elderly population. Non-vertebral fracture is significantly reduced in patients who are institutionalized when treated with appropriate doses of calcium (up to 1500mg) and vitamin D (400–800IU).[7779]

The addition of alendronate (10 mg/day) to calcium and vitamin D in a population of women in long-term residential care produced a greater increase in BMD and reduction in biochemical markers of bone turnover (bone alkaline phosphatase [Bone ALP], urine cross-linked N-terminal type I collagen telopeptide [NTX-1]) than calcium and vitamin D treatment alone.[80] The adverse effects of therapy were no greater than that of placebo (calcium and vitamin D). Data were not available of the effect on fracture incidence in this study.

The most recent data for the effect of HRT on non-vertebral fracture, reported in the WHI study, show a significant reduction of hip fracture.[72] The WHI study, however, has raised several concerns regarding long-term use of HRT and the commencement of HRT in elderly women. It has been concluded that in the population studied there was a predominance of adverse effects (such as increased risk for stroke, thrombosis, breast cancer, and coronary heart disease) over the beneficial effects (such as reduction in fractures and reduction in colorectal cancer). Therefore, a statement has been made by the WHI writing group that the combined preparation of HRT containing conjugated estrogen 0.625mg and medroxyprogesterone acetate 2.5mg is not a viable intervention for the primary prevention of chronic diseases.[72]

5.2.3 Comparative Treatment Studies

There are no published studies of direct comparisons of the various treatments in sufficiently large populations with fracture or QOL as outcomes. Those studies that are available indicate that alendronate has a greater effect on increasing BMD or reducing bone marker production than calcitonin[81,82] and risedronate (using variable doses)[83] and that little difference exists between etidronate and calcitriol.[84] A comparison of alendronate and raloxifene detected a significantly greater increase in BMD and decrease in markers of bone turnover by 6 months of treatment, which was maintained at 12 months.[85] Debate continues with regard to adverse effects, with some studies showing greater ulceration on endoscopic investigation with alendronate than with risedronate.[86] Other studies have failed to confirm this finding.[87]

5.2.4 Calcium and Vitamin D

Although calcium and vitamin D have been used as comparators in the majority of recent treatment studies[5764], they are also co-prescribed with other therapies. Patients are supplemented with calcium and vitamin D, in addition to that consumed in their diet, in order to bring their total daily intake to calcium 1500mg and vitamin D 400–800IU. It is important that adequate calcium and vitamin D supplementation is co-prescribed when therapies such as alendronate and risedronate are recommended.

5.2.5 Parathyroid Hormone

A recombinant human parathyroid hormone (1–34), teriparatide, has recently received approval for use in the treatment of osteoporosis in the US and Europe. This is given by daily subcutaneous injections (preferably at night) over a maximum of 18 months. Using the currently recommended dose of teriparatide of 20 μg/day, significant increases in mean lumbar spine (8.6%) and femoral neck (2.1%) BMD were observed compared with placebo.[88] New vertebral fractures decreased by 65%; however, there was no significant decrease in hip fracture. This new treatment is anabolic, resulting in a significant increase in bone formation.[88] Associated with this increase in bone formation is a significant increase in the serum biochemical marker of collagen formation, amino terminal pro-peptide of type 1 collagen (P1NP), within 1 month of commencing treatment. Teriparatide is the most expensive drug available to treat osteoporosis, costing £300 ($US600) per month (2004 values), and so detailed cost-benefit analyses will need to be performed to establish its place in overall management. It is likely that it will be reserved for patients with the most severe osteoporosis that does not, or is not likely to, respond to the antiresorptive therapies.

One difficulty that exists when analyzing the currently available studies and literature of the osteoporotic population is the lack of a precise estimate for a therapeutic effect in terms of fracture reduction associated with each treatment. All of the available clinical trials have different patient enrollment criteria, involve different study populations, and have different fracture incidence and prevalence in the control populations. To obtain a precise therapeutic effect estimate would require an extremely large population database and at present this is not feasible. As a result, estimates of the cost effectiveness of treatment can be based on optimistic or best-case scenarios (50% reduction in hip fracture) or conservative estimates (35% reduction in hip fracture). Further work is clearly required to improve the value of research in this area.

6. Additional Evidence for Therapeutic Efficacy

6.1 Biochemical Markers of Bone Metabolism

Several interventions have been shown to reduce the incidence of fractures; however, the optimal response and duration of therapy is still unknown. Few data are available on the rate of adherence to treatment, the rate of response, and the potential mechanisms to improve response to interventions. Biochemical markers of bone turnover are available to facilitate follow-up assessments of patients receiving antiresorptive treatments for osteoporosis; they can be used to detect patients who do not adhere to or whose symptoms do not respond to treatment.[89] Resorption and formation markers that are readily available are listed in table IV. Markers of resorption are an excellent reflection of osteoclast activity and since the majority of interventions that are being assessed act by affecting osteoclast activity, the measurement of these markers enable prediction of a reduction in fracture risk.[90] The availability of serum markers of bone resorption with significantly reduced biological and measurement variability, compared with urine measurements, makes it possible to follow changes with treatment with increasing accuracy. The magnitude and timing of reduction in bone turnover (within weeks) is a significant advantage compared with the slower changes in repeated BMD measurement or awaiting presentation with clinical fracture as an indication of intervention efficacy.[91] Early changes in markers of bone turnover in response to bisphosphonates predict the subsequent increase in BMD with high sensitivity, specificity, and predictive values.[92]
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Table IV

Biochemical markers of bone metabolism

A recent publication used a decision-analysis tree with Markov modeling to compare treatment strategies with and without measurement of serum markers of bone turnover at 3 months of treatment with bisphosphonates.[93] This analysis concluded that follow-up using biochemical markers of bone metabolism in women with osteoporosis over a 5-year period increases the effectiveness of treatment. Since a serum biochemical measure of resorption costs £13.50 on average per measurement, compared with £80 for a BMD measurement, and a year’s therapy with alendronate plus calcium and vitamin D costs £333 (2004 values) [personal observation], the potential economic benefit of using a biochemical measurement of resorption to detect noncompliance and nonresponse to therapy is large. In the UK, patients often deny problems with compliance or concordance unless an objective assessment of ineffective treatment is available and repeat prescriptions going unused incur continuing drug costs. Long-term persistence with bisphosphonate treatment is important and this has been significantly improved in patients treated with risedronate by physician reinforcement using verbal feedback of a good response to therapy defined by bone marker measurement.[94]

7. Intervention Thresholds for Osteoporosis

Determining intervention thresholds for osteoporosis is difficult, and there are few published studies to help with decisions regarding intervention. The diagnostic thresholds proposed in the past (table I) that were based on BMD score have several problems including the inability to identify all individuals who have a fracture;[95] more recent suggestions have been made that intervention should be based on absolute risk of fracture in a manner similar to the recommendations for lipid-lowering therapy. The data to make such calculations are not available in many countries and so estimates that are available have used data from Sweden, where long-term probabilities of osteoporotic fractures are available[96] and costed benefits in US dollars. In the Markov model,[93] mentioned in section 6, all osteoporotic fractures were included and the morbidity arising from a fracture was given a specific weighting.[97] The effects of an intervention costing $US500/year (£333/year) [the annual cost of treatment with alendronate plus calcium and vitamin D], given for 5 years have been modeled.[97] A threshold for cost effectiveness of $US60 000 per quality-adjusted life year (QALY) gained was used and costs of added years were excluded in a sensitivity analysis for which a threshold value of $US30 000 per QALY was used. The lower the cost of the intervention cost and the higher the effectiveness of that intervention, the lower the age of the person for which the intervention becomes cost effective.[98] Assuming that all osteoporotic fractures decrease by 35% (a conservative estimate), intervention becomes cost effective when treatment is targeted to women ≥65 years of age This modeling suggests that the available treatments that have a significant effect on fracture, as discussed in section 5, can be cost-effectively targeted to individuals who are at a moderately increased risk for fractures; those at the highest risk will obtain greatest benefits from treatment.

8. Conclusions

Osteoporosis is a common disorder that is associated with a significant increase in fracture risk, and treatment is available that can significantly modify disease progression. Demographic changes throughout the world are resulting in aging populations, which will result in a higher prevalence of osteoporosis and associated fractures. The financial and healthcare costs of osteoporosis are liable to increase dramatically for future generations unless appropriate steps are taken to prevent and treat the deterioration of BMD and osteoporosis-related fractures.

There are several therapies available that have been shown by meta-analyses to be effective in reducing vertebral (vitamin D with calcium, raloxifene, calcitonin, etidronate, risedronate, alendronate) and non-vertebral (alendronate, risedronate) fractures. In addition, new data from prospective studies of HRT indicate that over a 5- to 6-year period HRT has a significant effect on reducing vertebral and non-vertebral fracture, but raise concerns regarding detrimental effects of long-term treatment with HRT. Cost-analysis modeling using QALY as an assessment tool indicates that intervention is cost effective, depending on the cost of the intervention and the effectiveness of the treatment. It would appear prudent to recommend the use of the most potent therapies (alendronate, risedronate) in those at the highest risk of fracture, including patients who have experienced a recent fracture and those with the lowest BMD values at hip and spine. In certain cases, for instance patients with a modest reduction in bone mass, those with a reduction in vertebral BMD only, or in selected populations such as the housebound/institutionalized elderly, it is more cost effective to choose one of the other lower cost therapies that have a slightly lower therapeutic efficacy but an acceptable cost effectiveness (e.g. etidronate, calcium, and vitamin D).

Serious consideration should be given to the use of biochemical markers as tools to optimize therapeutic efficacy. There is a large evidence base indicating (i) that the measurement of a serum marker of bone metabolism (carboxy terminal telopeptide [CTX], Bone ALP, and P1NP) is highly indicative of a response to treatment; and (ii) that a decrease in a marker following the initiation of therapy can predict outcome in terms of both BMD change and fracture reduction. The measurement of bone markers can reduce the requirement for BMD estimation and can prove cost effective by ensuring persistence of therapy during the long-term management of patients with osteoporosis.

Stakeholders who are responsible for the provision of healthcare need to be aware of the ever-increasing data regarding osteoporosis. Detailed analyses of the epidemiological, social and medical impact of the disease, as well as evidence-based therapeutics, exist for osteoporosis. The increasing healthcare burden and availability of effective treatments make osteoporosis an excellent candidate for disease management programs.

Acknowledgements

There were no sources of external funding used to assist in preparation of this manuscript. The author has no conflicts of interest related to this manuscript. The author is happy to recognize that over the past 10 years he has lectured for and received grant funding from Boehringher Ingelheim, Lilly, MSD, Novartis, Proctor & Gamble, Roche, and Sanofi.

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