Osteoporosis International

, Volume 28, Issue 7, pp 2177–2186 | Cite as

Acute bone changes after lower limb amputation resulting from traumatic injury

  • D. A. BembenEmail author
  • V. D. Sherk
  • W. J. J. Ertl
  • M. G. Bemben
Original Article



Bone health is critical for lower limb amputees, affecting their ability to use a prosthesis and their risk of osteoporosis. We found large losses in hip bone mineral density (BMD) and in amputated bone strength in the first year of prosthesis use, suggesting a need for load bearing interventions early post-amputation.


Large deficits in hip areal BMD (aBMD) and residual limb volumetric BMD (vBMD) occur after lower limb amputation; however, the time course of these bone quality changes is unknown. The purpose of this study was to quantify changes in the amputated bone that occur during the early stages post-amputation.


Eight traumatic unilateral amputees (23–53 years) were enrolled prior to surgery. Changes in total body, hip, and spine aBMD (dual-energy X-ray absorptiometry); in vBMD, stress-strain index (SSI), and muscle cross-sectional area (MCSA) (peripheral QCT); and in bone turnover markers were assessed after amputation prior to prosthesis fitting (pre-ambulatory) and at 6 and 12 months walking with prosthesis.


Hip aBMD of the amputated limb decreased 11–15%, which persisted through 12 months. The amputated bone had decreases (p < 0.01) in BMC (−26%), vBMD (−21%), and SSI (−25%) from pre-ambulatory to 6 months on a prosthesis, which was maintained between 6 and 12 months. There was a decrease (p < 0.05) in the proportion of bone >650 mg/cm3 (58 to 43% of total area) or >480 mg/cm3 (65% to 53%), suggesting an increase in cortical porosity after amputation. Bone alkaline phosphatase and sclerostin were elevated (p < 0.05) at pre-ambulatory and then decreased towards baseline. Bone resorption markers were highest at surgery and pre-ambulatory and then progressively decreased (p < 0.05).


Rapid and substantial losses in bone content and strength occur early after amputation and are not regained by 12 months of becoming ambulatory. Early post-amputation may be the most critical window for preventing bone loss.


Bone density Bone geometry Bone remodeling Prosthesis Trauma 



This study was supported by a Department of Defense US Army Medical Research and Materiel Command Grant Award Number W81XWH-09-1-0641.

Compliance with ethical standards

This study was approved by the University of Oklahoma Health Sciences Center Institutional Review Board, and patients gave written informed consent prior to participation.

Conflict of interest

Debra Bemben, Vanessa Sherk, and Michael Bemben declare they have no conflict of interest.

William Ertl received speaker fees from Acelity/KCI, not related to this work.

Supplementary material

198_2017_4018_MOESM1_ESM.tif (146 kb)
Supplementary Fig 1. Study Protocol Timeline Black arrows indicate average duration for post-amputation measurement time points (TIFF 146 kb)
198_2017_4018_MOESM2_ESM.tif (231 kb)
Supplementary Fig 2. pQCT Measurement Sites on Residual and Intact Limbs (TIFF 231 kb)
198_2017_4018_MOESM3_ESM.tif (2.1 mb)
Supplementary Fig 3. Study Enrollment Flow (TIFF 2123 kb)
198_2017_4018_MOESM4_ESM.doc (34 kb)
Supplemental Table 1 (DOC 33 kb)
198_2017_4018_MOESM5_ESM.doc (36 kb)
Supplementary Table 2 (DOC 36 kb)


  1. 1.
    Rittweger J, Simunic B, Bilancio G et al (2009) Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment. Bone 44:612–618CrossRefPubMedGoogle Scholar
  2. 2.
    Morgan JLL, Heer M, Hargens AR et al (2014) Sex-specific responses of bone metabolism and renal stone risk during bed rest. Physiol Rep 2:e12119. doi: 10.14814/phy2.12119 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19:1006–1012CrossRefPubMedGoogle Scholar
  4. 4.
    Esquenazi A, DiGiacomo R (2001) Rehabilitation after amputation. J Am Podiatr Med Assoc 91:13–22CrossRefPubMedGoogle Scholar
  5. 5.
    Davies B, Datta D (2003) Mobility outcome following unilateral lower limb amputation. Prosthetics Orthot Int 27:186–190CrossRefGoogle Scholar
  6. 6.
    Perry J (2004) Amputee gait. In: Smith DG, Michael JW, Bowker JH (eds) Atlas of amputations and limb deficiencies: surgical, prosthetic, and rehabilitation principles. American Academy of Orthopaedic Surgeons, Rosemont, IL, pp 367–384Google Scholar
  7. 7.
    Robling AG, Turner C (2009) Mechanical signaling for bone modeling and remodeling. Crit Rev Eukaryot Gene Expr 19:219–338CrossRefGoogle Scholar
  8. 8.
    Kulkarni J, Adams J, Thomas E, Silman A (1998) Association between amputation, arthritis and osteopenia in British male war veterans with major lower limb amputations. Clin Rehabil 12:348–353CrossRefPubMedGoogle Scholar
  9. 9.
    Leclerq MM, Bonidan O, Haaby E, Pierrejean C, Sengler J (2003) Study of bone mass with dual energy x-ray absorptiometry in a population of 99 lower limb amputees. Annales de Readaptation et de Medicine Physique 46:24–30CrossRefGoogle Scholar
  10. 10.
    Rush PJ, Wong JSW, Kirsh J, Devlin M (1994) Osteopenia in patients with above knee amputation. Arch Phys Med Rehabil 75:112–115PubMedGoogle Scholar
  11. 11.
    Meerkin J, Parker T (2002) Bone mineral apparent density of transfemoral amputees. Proceedings of the Australian Conference of Science and Medicine in Sport: Sports Medicine and Science at the ExtremesGoogle Scholar
  12. 12.
    Royer T, Koenig M (2005) Joint loading and bone mineral density in persons with unilateral, trans-tibial amputation. Clin Biomech 20:1119–1125CrossRefGoogle Scholar
  13. 13.
    Yazicioglu K, Tugcu I, Yilmaz B, Goktepe AS, Mohur H (2008) Osteoporosis: a factor on residual limb pain in traumatic trans-tibial amputations. Prosthetics Orthot Int 32:172–178CrossRefGoogle Scholar
  14. 14.
    Tugcu I, Safaz I, Yilmaz B, Goktepe AH, Taskaynatan MA, Yazicioglu K (2009) Muscle strength and bone mineral density in mine victims with transtibial amputation. Prosthetics Orthot Int 33:299–306CrossRefGoogle Scholar
  15. 15.
    Flint JH, Wade AM, Stocker DJ, Pasquina PF, Howard RS, Potter BK (2014) Bone mineral density loss after combat-related lower extremity amputation. J Orthop Trauma 28:238–244CrossRefPubMedGoogle Scholar
  16. 16.
    Smith E, Comiskey C, Carroll A, Ryall N (2011) A study of bone mineral density in lower limb amputees at a National Prosthetics Center. J Prosthet Orthot 23:14–20CrossRefGoogle Scholar
  17. 17.
    Gonzalez EG, Matthews MM (1980) Femoral fractures in patients with lower extremity amputations. Arch Phys Med Rehabil 61:276–280PubMedGoogle Scholar
  18. 18.
    Sherk VD, Bemben MG, Bemben DA (2008) Bone density and bone geometry in transtibial and transfemoral amputees. J Bone Miner Res 23:1449–1457CrossRefPubMedGoogle Scholar
  19. 19.
    Sherk VD, Bemben MG, Bemben DA (2010) Interlimb muscle and fat comparisons in persons with lower limb amputations. Arch Phys Med Rehabil 91:1077–1081CrossRefPubMedGoogle Scholar
  20. 20.
    Miller WC, Speechley M, Deathe B (2001) The prevalence and risk factors of falling and fear of falling among lower extremity amputees. Arch Phys Med Rehabil 82:1031–1037CrossRefPubMedGoogle Scholar
  21. 21.
    Pauley T, Devlin M, Heslin K (2006) Falls sustained during inpatient rehabilitation after lower limb amputation: prevalence and predictors. Am J Phys Med Rehabil 85(6):521–532 quiz, 533-5CrossRefPubMedGoogle Scholar
  22. 22.
    Robling AG, Niziolek PJ, Baldridge LA et al (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875CrossRefPubMedGoogle Scholar
  23. 23.
    Lin C, Jiang X, Dai Z et al (2009) Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24:1651–1661CrossRefPubMedGoogle Scholar
  24. 24.
    Frings-Meuthen P, Boehme G, Liphardt AM, Baecker N, Heer M, Rittweger J (2013) Sclerostin and DKK1 levels during 14 and 21 days of bed rest in healthy young men. J Musculoskelet Neuronal Interact 13:45–52PubMedGoogle Scholar
  25. 25.
    Belavy DL, Baecker N, Armbrecht G et al (2016) Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J Bone Miner Metab 34:354–365CrossRefPubMedGoogle Scholar
  26. 26.
    Gaudio A, Pennisi P, Bratengeier C et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253CrossRefPubMedGoogle Scholar
  27. 27.
    Sarahrudi K, Thomas A, Albrecht C, Aharinejad S (2012) Strongly enhanced levels of sclerostin during human fracture healing. J Orthop Res 30:1549–1555CrossRefPubMedGoogle Scholar
  28. 28.
    Cox G, Einhorn TA, Tzioupis C, Giannoudis PV (2010) Bone-turnover markers in fracture healing. J Bone Joint Surg 92-B:329–334CrossRefGoogle Scholar
  29. 29.
    Krusenstjerna-Hafstrom T, Rasmussen MH, Raschke M, Govender S, Madsen J, Christiansen JS (2011) Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth hormone (GH) or placebo injections. Growth Hormon IGF Res 21:331–335CrossRefGoogle Scholar
  30. 30.
    Moghaddam A, Müller U, Roth HJ, Wentzensen A, Grützner PA, Zimmermann G (2011) TRACP 5b and CTX as osteological markers of delayed fracture healing. Injury 42:758–764CrossRefPubMedGoogle Scholar
  31. 31.
    Szulc P, Bauer DC, Eastell R (2013) Biochemical markers of bone turnover in osteoporosis. In: Rosen CJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 8th edn. Wiley-Blackwell, Ames Iowa, pp 297–306CrossRefGoogle Scholar
  32. 32.
    Seeman E (2013) Age- and menopause-related bone loss compromise cortical and trabecular microstructure. J Gerontol A Biol Sci Med 68:1218–1225CrossRefGoogle Scholar
  33. 33.
    Rissanen JP, Suominen MI, Peng Z, Halleen JM (2008) Secreted tartrate-resistant acid phosphatase 5b is a marker of osteoclast number in human osteoclast cultures and the rat ovariectomy model. Calcif Tissue Int 82:108–115CrossRefPubMedGoogle Scholar
  34. 34.
    Holick MF (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19:73–78CrossRefPubMedGoogle Scholar
  35. 35.
    Schousboe JT, Shepherd JA, Bilezikian JP, Baim S (2013) Executive summary of the 2013 International Society for Clinical Densitometry position development conference on bone densitometry. J Clin Densitom 16:455–466CrossRefPubMedGoogle Scholar
  36. 36.
    IOM (Institute of Medicine) (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DCGoogle Scholar
  37. 37.
    Ramirez JF, Isaza JA, Mariaka I, Velez JA (2011) Analysis of bone demineralization due to the use of exoprosthesis by comparing Young’s modulus of the femur in unilateral amputees. Prosthetics Orthot Int 35:459–466CrossRefGoogle Scholar
  38. 38.
    Lam FMH, Bui M, Yang FZH, Pang MYC (2016) Chronic effects of stroke on hip bone density and tibial morphology: a longitudinal study. Osteoporosis Int 27:591–603CrossRefGoogle Scholar
  39. 39.
    Kostovski E, Hjeltnes N, Eriksen EF, Kolset SO, Iversen PO (2015) Differences in bone mineral density, markers of bone turnover and extracellular matrix and daily life muscular activity among patients with recent motor-incomplete versus motor-complete spinal cord injury. Calcif Tissue Int 96:145–154CrossRefPubMedGoogle Scholar
  40. 40.
    Coupaud S, McLean AN, Purcell M, Fraser MH, Allan DB (2015) Decreases in bone mineral density at cortical and trabecular sites in the tibia and femur during the first year of spinal cord injury. Bone 74:69–75CrossRefPubMedGoogle Scholar
  41. 41.
    Melton LJ III, Khosla S, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL (2000) Cross-sectional versus longitudinal evaluation of bone loss in men and women. Osteoporosis Int 11:592–599CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  • D. A. Bemben
    • 1
    Email author
  • V. D. Sherk
    • 2
  • W. J. J. Ertl
    • 3
  • M. G. Bemben
    • 1
  1. 1.Bone Density Research Laboratory, Department of Health and Exercise ScienceUniversity of OklahomaNormanUSA
  2. 2.Department of Medicine, Division of Endocrinology, Metabolism and DiabetesUniversity of Colorado at Denver Anschutz Medical CampusAuroraUSA
  3. 3.Department of Orthopedic SurgeryUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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