Draft Recommendations. Pharmacotherapy for the Prevention of Repeated Fractures in Patients with Osteoporosis after Surgical Treatment of Pathologic Proximal Femur Fracture


Treatment of pathologic proximal femur fractures complicating the course of systemic osteoporosis is most often limited by surgical intervention as until now trauma and orthopaedic surgeons have no concrete recommendations on pharmacologic correction of metabolism disorders typical to the pathology, that aggravate in the postoperative period due to operative trauma. Proposed draft recommendations are a part of National clinical recommendations “Treatment for pathologic fractures of skeleton bones complicating the course of osteoporosis”. This issue of recommendations is only applicable to pharmacotherapy directed to the correction of bone tissue remodeling with regard for the fracture localization and volume of surgical intervention. Present recommendations are intended for the improvement of patients’ life quality, reduction of present and future losses from pathologic fracture as well as the prevention of repeated fractures.

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About the authors

S. P Mironov

N.N. Priorov Central Institute of Traumatology and Orthopaedics

Moscow, Russia

S. S Rodionova

N.N. Priorov Central Institute of Traumatology and Orthopaedics

Email: rod06@inbox.ru
Moscow, Russia

A. N Torgashin

N.N. Priorov Central Institute of Traumatology and Orthopaedics

Moscow, Russia


  1. Johnell O., Kanis J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 2006; 17 (12): 1726-33.
  2. Singer A., Exuzides A., Spangler L. et al. Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin. Proc. 2015; 90 (1): 53-62.
  3. Kanis J.A. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002; 359 (9321): 1929-36.
  4. Eiben G., Dey D.K., Rothenberg E. et al. Obesity in 70-year-old Swedes: secular changes over 30 years. Int. J. Obes. (Lond). 2005; 29 (7): 810-7.
  5. Gullberg B., Johnell O., Kanis J.A. World-wide projections for hip fracture. Osteoporos. Int. 1997; 7 (5): 407-13.
  6. Leslie W.D., Morin S.N. Osteoporosis epidemiology 2013: implications for diagnosis, risk assessment, and treatment. Curr. Opin. Rheumatol. 2014; 26 (4): 440-6.
  7. Ikeda K., Ogata E. Modulation of bone remodeling by active vitamin D: Its role in treatment of osteoporosis. Мech. Ageing Dev. 2000; 116 (2-3): 103-11.
  8. Kim S.C., Kim M., Sanf_lix-Gimeno G. et al. Use of osteoporosis medications after hospitalization for hip fracture: a cross-national study. Am. J. Med. 2015; 128 (5): 519-26.
  9. Solomon D.H., Johnston S.S., Boytsov N.N. et al. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J. Bone Miner. Res. 2014; 29 (9): 1929-37.
  10. Scaglione M., Fabbri L., Di Rollo F. et al. The second hip fracture in osteoporotic patients: not only an orthopedic matter. Clin. Cases Miner. Bone Metab. 2013;10 (2): 124-8.
  11. Kanis J.A., McCloskey E., Branco J. et al. Goal-directed treatment of osteoporosis in Europe. Osteoporos. Int. 2014; 25 (11): 2533-43.
  12. Seeman E., Compston J., Adachi J. et al. Non-compliance: the Achilles’ heel of anti-fracture efficacy. Osteoporos. Int. 2007; 18 (6): 711-9.
  13. Kim S.C., Kim M.S., Sanf_lix-Gimeno G. et al. Use of osteoporosis medications after hospitalization for hip fracture: a crossnational study. Am. J. Med. 2015; 128 (5): 519-26.
  14. Cranney A., Wells G., Willan A. et al. Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr. Rev. 2002; 23 (4): 508-16.
  15. Wells G.A., Cranney A., Peterson J. et al. Alendronate for the primary and secondary prevention of osteoporotic fr actures in postmenopausal women. Cochrane Database Syst. Rev. 2008; (1): CD001155.
  16. Larsson S. Time to invest in a “fracture liaison nurse”! Injury. 2007; 38 (11): 1225-6.
  17. Melton L.J. 3rd. Adverse outcomes of osteoporotic fractures in the general population. J. Bone Miner. Res. 2003; 18 (6): 1139-41.
  18. Garnero P., Sornay-Rendu E., Claustrat B., Delmas P.D. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J. Bone Miner. Res. 2000; 15 (8): 1526-36.
  19. Camacho P.M., Petak S.M., Binkley N. et al. American association of clinical endocrinologists and American college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis - 2016. Endocr. Pract. 2016; 22 (Suppl 4): 1-42.
  20. Borghi L., Schianchi T., Meschi T. et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N. Engl. J. Med. 2002; 346 (2): 77-84.
  21. Родионова С.С., Хакимов У.Р. Безопасность долгосрочного использования альфакальцидола при первичных формах системного остеопороза у мужчин. Клиническая геронтология. 2016; 5-6 (22): 27-33.
  22. Родионова С.С., Буклемишев Ю.В. Эффективность золедроновой кислоты у пациентов с системным остеопорозом и проблема «неответчиков» лечения. Вестник травматологии и ортопедии им. Н.Н. Приорова. 2015; 4: 39-43.
  23. Burch J., Rice S., Yang H. et al. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high- risk groups. Health Technol. Assess. 2014; 18 (11): 1-180.
  24. Оглоблин Н.А., Спиричев В.Б., Батурин А.К. О потреблении населением России кальция с пищей. Вопросы питания. 2005; 5: 14-7.
  25. Varenna M., Binelli L., Casari S. et al. Effects of dietary calcium intake on body weight and prevalence of osteoporosis in early postmenopausal women. Am. J. Clin. Nutr. 2007; 86 (3): 639-44.
  26. Prince R.L., Devine A., Dhaliwal S.S. et al. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo- controlled trial in elderly women. Arch. Intern. Med. 2006; 166 (8): 869-75.
  27. Prentice R.L., Pettinger M.B., Jackson R.D. et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos. Int. 2013; 24 (2): 567-80.
  28. Tang B.M., Eslick G.D., Nowson C. et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007; 370 (9588): 657-66.
  29. Micha_lsson K., Melhus H., Warensj_ Lemming E. et al. Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ. 2013; 346: f228.
  30. Heaney R.P. Quantifying human calcium absorption using pharmacokinetic methods. J. Nutr. 2003; 133 (4): 1224-6.
  31. Buclin T., Jacquet A.F., Burckhardt P. Intestinal absorption of calcium gluconate and oseine-mineral complex: an evaluation by conventional analyses. Schweiz. Med. Wochenschr. 1986; 116 (50): 1780-3 (in French).
  32. Fernandez-Pareja A., Hern_ndez-Blanco E., P_rez-Mace- da J.M. et al. Prevention of osteoporosis. Four year follow- up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite compound. Clin. Drug Investig. 2007; 27 (4): 227-32.
  33. Annefeld M., Caviezel R., Schacht E., Schicketanz K.H. The influence of ossein-hydroxyapatite compound (_Ossopan‘) on the healing of a bone defect. Curr. Med. Res. Opin. 1986;10 (4): 241-50.
  34. Ciria-Recasens M., Blanch-Rubi_ J., Coll-Batet M. et al. Comparison of the effects of ossein-hydroapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open- label, parallel-group, controlled, prospective study. Clin. Drug Investig. 2011; 31 (12): 817-24.
  35. Castelo-Branco C., Ciria-Recasens M., Cancelo-Hidal- go M.J. et al. Efficacy of ossein-hydroxyapatit complex compared with calcium carbonate to prevent bone loss: a meta-analysis. Menopause. 2009; 16 (5): 984-91.
  36. Wacker M., Holick M.F. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013; 5 (1): 51-108.
  37. Pisani P., Renna M.D., Conversano F. et al. Fracture risk factors and impact. Major osteoporotic fragility fractures: Risk factor updates and societal impact. World J. Orthop. 2016; 7 (3): 171-81.
  38. Bischoff-Ferrari H.A., Dawson-Hughes B., Baron J.A. et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am. J. Clin. Nutr. 2007; 86 (6): 1780-90.
  39. Nuti R., Bianchi G., Brandi M.L. et al. Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis. Rheumatol. Int. 2006; 26 (5): 445-53.
  40. Lau K.H., Baylink D.J. Treatment of 1,25(OH)2D3 (D-hormone) deficiency/resistance with D-hormone and analogs. Osteologie. 2001; 10: 28-39.
  41. Rix M., Eskildsen P., Olgaard K. Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol. Dial Transplant. 2004; 19 (4): 870-6.
  42. Schacht E., Richy F., Reginster J.Y. The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures. J. Musculoskelet. Neuronal. Interact. 2005; 5 (3): 273-84.
  43. Shiraishi A., Takeda S., Masaki T. et al. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen. J. Bone Miner. Res. 2000; 15 (4): 770-9.
  44. Sakhaee K., Maalouf N., Kumar R. et al. Nephrolithiasis- associated bone disease: pathogenesis and treatment options. Kidney Int. 2011; 79 (4): 393-403.
  45. Шварц Г.Я. Фармакотерапия остеопороза. М.: Медицинское информационное агентство; 2002.
  46. Looker A.C., Melton L.J. 3rd, Borrud L.G., Shepherd J.A. Changes in femur neck bone density in US adults between 1988-1994 and 2005-2008: demographic patterns and possible determinants. Osteoporos. Int. 2012; 23 (2): 771-80.
  47. Leslie W.D., Lix L.M., Yogendran M.S. et al. Temporal trends in obesity, osteoporosis treatment, bone mineral density, and fracture rates: a population-based historical cohort study. J. Bone Miner. Res. 2014; 29 (4): 952-9.
  48. Родионова С.С., Нуждин В.И., Морозов А.К. и др. Остеопороз как фактор риска асептической нестабильности при эндопротезировании тазобедренного сустава. Вестник травматологии и ортопедии им. Н.Н. Приорова. 2007; 2: 35-40.
  49. Grant A., Avenell A., Campbell M.K. et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo- controlled trial. Lancet. 2005; 365 (9471): 1621-8.
  50. Johnell O., Nilsson B., Obrant K., Sernbo I. Age and sex patterns of hip fracture - changes in 30 years. Acta Orthop. Scand. 1984; 55: 290-2.
  51. Karlsson M., Hannavy K., Higgins C.F. A sequence-specific function for the N-terminal signal-like sequence of the TonB protein. Mol. Microbiol. 1993; 8 (2): 379-88.
  52. Nishioka T., Yagi S., Mitsuhashi T. et al. Alendronate inhibits periprosthetic bone loss around uncemented femoral components. J. Bone Miner. Metab. 2007; 25 (3): 179-83.
  53. Hallan G., Lie S.A., Havelin L.I. High wear rates and extensive osteolysis in 3 types of uncemented total hip arthroplasty: a review of the PCA, the Harris Galante and the Profile/Tri-Lock Plus arthroplasties with a minimum of 12 years median follow-up in 96 hips. Acta Orthop. 2006; 77 (4): 575-84.
  54. Arabmotlagh M., Rittmeister M., Hennigs T. Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective randomized double-blind study. J. Orthop. Res. 2006; 24 (7): 1336-41.
  55. Lyles K.W., Colon-Emeric C.S., Magaziner J.S. et al. Zoledronic acid inreducing clinical fracture and mortal- ity after hip fracture. N. Engl. J. Med. 2007; 357 (18); 1799- 809.
  56. Cosman F., Cauley J., Eastell R. et al. Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J. Clin. Endocrinol. Met. 2014; 99 (12): 4546-54.
  57. Cosman F., Beur S. J., LeBoff M.S. et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos. Int. 2014; 25 (10): 2359-81.
  58. Colon-Emeric C., Nordsletten L., Olson S. et al. Association between timing of zoledronic acid infusion and hip frac- ture healing. Osteoporos. Int. 2011; 22 (8): 2329-36.
  59. Amanat N., McDonald M., Godfrey C. et al. Optimal timing of a singledose of zoledronic acid to increase strength in rat fracture repair. J. Bone Miner. Res. 2007; 22 (6): 867-76.
  60. Egermann M., Goldhahn J., Schneider E. Animal models for fracture treatment in osteoporosis. Osteoporos. Int. 2005; 16 (Suppl 2): S129-38.
  61. Durie B.G., Katz M., Crowley J. Osteonecrosis of the jaw and bisphosphonates. N. Engl. J. Med. 2005; 353 (1): 99- 102.
  62. Gedmintas L., Solomon D.H., Kim S.C. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J. Bone Miner. Res. 2013; 28 (8): 1729-37.
  63. Dixon W.G., Solomon D.H. Bisphosphonates and esophageal cancer - a pathway through the confusion. Nat. Rev. Rheumatol. 2011; 7 (6): 369-72.
  64. Grbic J.T., Landesberg R., Lin S.Q. et al. Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial. J. Am. Dent. Assoc. 2008; 139 (1): 32-40.
  65. Imaz I., Zegarra P., Gonz_lez-Enr_quez J. et al. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta- analysis. Osteoporos. Int. 2010; 21 (11): 1943-51.
  66. Schilcher J., Aspenberg P. Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop. 2009; 8 (4): 413-5.
  67. Gerstenfeld L.C., Sacks D.J., Pelis M. et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J. Bone Miner Res. 2009; 24 (2): 196-208.
  68. Cummings S.R., San Martin J., McClung M.R. et al. FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 2009; 361 (8): 756-65.
  69. Kendler D., Roux C., Benhamou C.L. et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J. Bone Miner. Res. 2010; 25 (1): 72-81.
  70. Massart F., Brandi M. Genetics of the bone response to bisphosphonate treatments. Clin. Cases Miner. Bone Metab. 2009; 6 (1): 50-4.
  71. Miller P.D. A review of the efficacy and safety of denosumab in postmenopausal women with osteoporosis. Ther. Adv. Musculoskelet. Dis. 2011; 3 (6): 271-82.
  72. Choi N.K., Solomon D.H., Tsacogianis T.N. et al. Comparative safety and effectiveness of denosumab versus zoledronic acid in patients with osteoporosis: a cohort study. J. Bone Miner. Res. 2017; 32 (3): 611-7.
  73. Reid I.R. Denosumab after 8 years. Osteoporos. Int. 2015; 26 (12): 2759-61.
  74. Gagnon C., Li V., Ebeling P.R. Osteoporosis in men: its pathophysiology and the role of teriparatide in its treatment. Clin. Interv. Aging. 2008; 3 (4): 635-45.
  75. Bhandari M., Jin L., See K. et al. Does teriparatide improve femoral neck fracture healing: results from a randomized placebo-controlled trial. Clin. Orthop. Relat. Res. 2016; 474 (5): 1234-44.
  76. Aspenberg P., Malouf J., Tarantino U. effects of teriparatide compared with risedronate on recovery after pertrochanteric hip fracture results of a randomized, active- controlled, double-blind clinical trial at 26 weeks. J. Bone Joint Surg. Am. 2016; 98 (22): 1868-78.
  77. Eriksen E.F., Keaveny T.M., Gallagher E.R., Krege J.H. Literature review: The effects of teriparatide therapy at the hip in patients with osteoporosis. Bone. 2014; 67: 246-56.
  78. Keaveny T.M., McClung M.R., Wan X. et al. Femoral strength in osteoporotic women treated with teriparatide or alendronate. Bone. 2012; 50 (1): 165-70.
  79. Oteo-_lvaro _., Matas J.A., Alonso-Farto J.C. Teriparatide (rh [1-34] PTH) improved osteointegration of a hemiarthroplasty with signs of aseptic loosening. Orthopedics. 2011; 34 (9): e574-7.
  80. Huang T.W., Chuang P.Y., Lin S.J. et al. Teriparatide improves fracture healing and early functional recovery in treatment of osteoporotic intertrochanteric fractures. Medicine (Baltimore). 2016; 95 (19): e3626.
  81. Huang T.W., Yang T.Y., Huang K.C. et al. Effect of teriparatide on unstable pertrochanteric fractures. Biomed. Res. Int. 2015; (2015): 568390.
  82. Ivaska K.K., Gerdhem P., Akesson K., Garnero P., Obrant K.J. Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women. J. Bone Miner. Res. 2007; 22 (8): 1155-64.
  83. Mandema J.W., Zheng J., Libanati C., Perez Ruixo J.J. Time course of bone mineral density changes with denosumab compared with other drugs in postmenopausal osteoporosis: a dose-response-based meta-analysis. J. Clin. Endocrinol. Metab. 2014; 99 (10): 3746-55.



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