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Effect of osteoporosis medications on fracture healing

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Abstract

Antiosteoporotic medications are often used to concurrently treat a patient’s fragility fractures and underlying osteoporosis. This review evaluates the existing literature from animal and clinical models to determine these drugs’ effects on fracture healing. The data suggest that these medications may enhance bone healing, yet more thorough prospective studies are warranted. Pharmacologic agents that influence bone remodeling are an essential component of osteoporosis management. Because many patients are first diagnosed with osteoporosis when presenting with a fragility fracture, it is critical to understand how osteoporotic medications influence fracture healing. Vitamin D and its analogs are essential for the mineralization of the callus and may also play a role in callus formation and remodeling that enhances biomechanical strength. In animal models, antiresorptive medications, including bisphosphonates, denosumab, calcitonin, estrogen, and raloxifene, do not impede endochondral fracture healing but may delay repair due to impaired remodeling. Although bisphosphonates and denosumab delay callus remodeling, they increase callus volume and result in unaltered biomechanical properties. Calcitonin increases cartilage formation and callus maturation, resulting in improved biomechanical properties. Parathyroid hormone, an anabolic agent, has demonstrated promise in animal models, resulting in accelerated healing with increased callus volume and density, more rapid remodeling to mature bone, and improved biomechanical properties. Clinical data with parathyroid hormone have demonstrated enhanced healing in distal radius and pelvic fractures as well as postoperatively following spine surgery. Strontium ranelate, which may have both antiresorptive and anabolic properties, affects fracture healing differently in normal and osteoporotic bone. While there is no effect in normal bone, in osteoporotic bone, strontium ranelate increases callus bone formation, maturity, and mineralization; forms greater and denser trabeculae; and improves biomechanical properties. Further clinical studies with these medications are needed to fully understand their effects on fracture healing in order to simultaneously treat fragility fractures and underlying osteoporosis.

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References

  1. Rebolledo BJ, Unnanuntana A, Lane JM (2011) A comprehensive approach to fragility fractures. J Orthop Trauma 25(9):566–573

    Article  PubMed  Google Scholar 

  2. Goldhahn J, Little D, Mitchell P et al (2010) Evidence for anti-osteoporosis therapy in acute fracture situations—recommendations of a multidisciplinary workshop of the International Society for Fracture Repair. Bone 46(2):267–271

    Article  CAS  PubMed  Google Scholar 

  3. Namkung-Matthai H, Appleyard R, Jansen J et al (2001) Osteoporosis influences the early period of fracture healing in a ratosteoporotic model. Bone 28:80–86

    Article  CAS  PubMed  Google Scholar 

  4. Wang JW, Li W, Xu SW et al (2005) Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model. Chin J Traumatol 8:111–116

    PubMed  Google Scholar 

  5. McClung MR, Grauer A, Boonen S et al (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370(5):412–420

    Article  CAS  PubMed  Google Scholar 

  6. Nakamura T, Shiraki M, Fukunaga M et al (2014) Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis—a double-blind, randomized, dose-finding study. Osteoporos Int 25:367–376

    Article  CAS  PubMed  Google Scholar 

  7. Soung DY, Gentile MA, Duong LT, Drissi H (2013) Effects of pharmacological inhibition of cathepsin K on fracture repair in mice. Bone 55(1):248–255

    Article  CAS  Google Scholar 

  8. Virk MS, Alaee F, Tang H et al (2013) Systemic administration of sclerostin antibody enhances bone repair in a critical-sized femoral defect in a rat model. J Bone Joint Surg Am 95(8):694–701

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY et al (2004) Effect of vitamin D on falls: a meta-analysis. JAMA 291(16):1999–2006

    Article  CAS  PubMed  Google Scholar 

  10. Gorter EA, Hamdy NA, Appelman-Dijkstra NM, Schipper IB (2014) The role of vitamin D in human fracture healing: a systemic review of the literature. Bone 64C:288–297

    Article  CAS  Google Scholar 

  11. Delgado-Martinez AD, Martinez ME, Carrascal MT, Rodriguez-Avial M, Munuera L (1998) Effect of 25-OH-vitamin D on fracture healing in elderly rats. J Orthop Res 16(6):650–653

    Article  CAS  PubMed  Google Scholar 

  12. Omeroglu H, Ates Y, Akkus O, Korkusuz F, Bicimoglu A, Akkas N (1997) Biomechanical analysis of the effects of single high-dose vitamin D3 on fracture healing in a healthy rabbit model. Arch Orthop Trauma Surg 116(5):271–274

    Article  CAS  PubMed  Google Scholar 

  13. Lindgren JU, Narechania RG, McBeath AA, Lange TA, DeLuca HF (1981) Effects of 1,24 dihydroxyvitamin D3 and calcitonin on fracture healing in adult rats. Clin Orthop Relat Res 160:304–308

    CAS  Google Scholar 

  14. Brumbaugh PF, Speer DP, Pitt MJ (1982) 1 Alpha, 25-dihydroxyvitamin D3 a metabolite of vitamin D that promotes bone repair. Am J Pathol 106(2):171–179

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kubo T, Shiga T, Hashimoto J, Yoshioka M, Honjo H, Urabe M et al (1999) Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet. J Steroid Biochem Mol Biol 68(5–6):197–202

    Article  CAS  PubMed  Google Scholar 

  16. Jingushi S, Iwaki A, Higuchi O, Azuma Y, Ohta T, Shida JI et al (1998) Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing. Endocrinology 139(4):1467–1473

    CAS  Google Scholar 

  17. Seo EG, Einhorn TA, Norman AW (1997) 24R,25-Dihydroxyvitamin D3: an essential vitamin D3 metabolite for both normal bone integrity and healing of tibial fracture in chicks. Endocrinology 138(9):3864–3872

    CAS  PubMed  Google Scholar 

  18. Kato A, Seo EG, Einhorn TA, Bishop JE, Norman AW (1998) Studies on 24R,25-dihydroxyvitamin D3: evidence for a nonnuclear membrane receptor in the chick tibial fracture-healing callus. Bone 23(2):141–146

    Article  CAS  PubMed  Google Scholar 

  19. Pedrozo HA, Schwartz Z, Rimes S et al (1999) Physiological importance of the 1,25(OH)2D3 membrane receptor and evidence for a membrane receptor specific for 24,25(OH)2D3. J Bone Miner Res 14(6):856–867

    Article  CAS  PubMed  Google Scholar 

  20. Saito M, Shiraishi A, Ito M, Sakai S, Hayakawa N, Mihara M et al (2010) Comparison of effects of alfacalcidol and alendronate on mechanical properties and bone collagen cross-links of callus in the fracture repair rat model. Bone 46(4):1170–1179

    Article  CAS  PubMed  Google Scholar 

  21. van Leeuwen JP, van Driel M, van den Bemd GJ, Pols HA (2001) Vitamin D control of osteoblast function and bone extracellular matrix mineralization. Crit Rev Eukaryot Gene Expr 11:199–226

    Article  PubMed  Google Scholar 

  22. Anderson PH, Atkins GJ (2008) The skeleton as an intracrine organ for vitamin D metabolism. Mol Asp Med 29:397–406

    Article  CAS  Google Scholar 

  23. van Driel M, Koedam M, Buurman CJ, Hewison M, Chiba H, Uitterlinden AG et al (2006) Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells. FASEB J 20:2417–2419

    Article  PubMed  CAS  Google Scholar 

  24. van Driel M, Koedam M, Buurman CJ, Roelse M, Weyts F, Chiba H et al (2006) Evidence that both 1 alpha,25-dihydroxyvitamin D-3 and 24-hydroxylated D-3 enhance human osteoblast differentiation and mineralization. J Cell Biochem 99:922–935

    Article  PubMed  CAS  Google Scholar 

  25. Fu L, Tang T, Miao Y, Hao Y, Dai K (2009) Effect of 1,25-dihydroxy vitamin D3 on fracture healing and bone remodeling in ovariectomized rat femora. Bone 44(5):893–898

    Article  CAS  PubMed  Google Scholar 

  26. Kogawa M, Anderson PH, Findlay DM, Morris HA, Atkins GJ (2010) The metabolism of 25(OH)vitamin D3 by osteoclasts and their precursors regulates the differentiation of osteoclasts. J Steroid Biochem Mol Biol 121:277–280

    Article  CAS  PubMed  Google Scholar 

  27. Mee AP, Hoyland JA, Braidman IP, Freemont AJ, Davies M, Mawer EB (1996) Demonstration of vitamin D receptor transcripts in actively resorbing osteoclasts in bone sections. Bone 18:295–299

    Article  CAS  PubMed  Google Scholar 

  28. Qi DY, Perkins SL, Kling SJ, Russell RG (1999) Divergent regulation of 1,25-dihydroxyvitamin D3 on human bone marrow osteoclastogenesis and myelopoiesis. J Cell Biochem 72:387–395

    Article  CAS  PubMed  Google Scholar 

  29. Thavarajah M, Evans DB, Kanis JA (1991) 1,25(OH)2D3 induces differentiation of osteoclast-like cells from human bone marrow cultures. Biochem Biophys Res Commun 176:1189–1195

    Article  CAS  PubMed  Google Scholar 

  30. Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B (2004) The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int 75(3):183–188

    Article  CAS  PubMed  Google Scholar 

  31. Brinker MR, O’Connor DP, Monla YT, Earthman TP (2007) Metabolic and endocrine abnormalities in patients with nonunion. J Orthop Trauma 21(8):557–570

    Article  PubMed  Google Scholar 

  32. Bolland MJ, Barber PA, Doughty RN et al (2008) Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 336:262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bolland MJ, Avenell A, Baron JA et al (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Steingrimsdottir L, Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G (2005) Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA 294(19):2336–2341

    Article  CAS  PubMed  Google Scholar 

  35. Sakuma M, Endo N, Oinuma T et al (2006) Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int 17:1608–1614

    Article  CAS  PubMed  Google Scholar 

  36. Russell RG (2011) Bisphosphonates: the first 40 years. Bone 49:2–19

    Article  CAS  PubMed  Google Scholar 

  37. Chapurlat RD, Palermo L, Ramsay P, Cummings SR (2005) Risk of fracture among women who lose bone density during treatment with alendronate. The fracture intervention. Osteoporos Int 16(7):842–848

    Article  CAS  PubMed  Google Scholar 

  38. McDonald MM, Dulai S, Godfrey C, Amanat N, Sztynda T, Little DG (2008) Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling. Bone 43(4):653–662

    Article  CAS  PubMed  Google Scholar 

  39. Matos MA, Tannuri U, Guarniero R (2010) The effect of zoledronate during bone healing. J Orthop Traumatol 11(1):7–12

    Article  PubMed  PubMed Central  Google Scholar 

  40. Amanat N, McDonald M, Godfrey C, Bilston L, Little D (2007) Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res 22(6):867–876

    Article  CAS  PubMed  Google Scholar 

  41. Li C, Mori S, Li J, Kaji Y, Akiyama T, Kawanishi J et al (2001) Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats. J Bone Miner Res 16(3):429–436

    Article  CAS  PubMed  Google Scholar 

  42. Fleisch H (2001) Can bisphosphonates be given to patients with fractures? J Bone Miner Res 16(3):437–440

    Article  CAS  PubMed  Google Scholar 

  43. Kurth AH, Eberhardt C, Muller S, Steinacker M, Schwarz M, Bauss F (2005) The bisphosphonate ibandronate improves implant integration in osteopenic ovariectomized rats. Bone 37:204–210

    Article  CAS  PubMed  Google Scholar 

  44. Chen B, Li Y, Yang X, Xu H, Xie D (2013) Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats. Osteoporos Int 24:2115–2121

    Article  CAS  PubMed  Google Scholar 

  45. Skripitz R, Johansson HR, Ulrich SD, Werner A, Aspenberg P (2009) Effect of alendronate and intermittent parathyroid hormone on implant fixation in ovariectomized rats. J Orthop Sci 14:138–143

    Article  CAS  PubMed  Google Scholar 

  46. Chen BL, Xie DH, Zheng ZM, Lu W, Ning CY, Li YQ et al (2011) Comparison of the effects of alendronate sodium and calcitonin on bone-prosthesis osseointegration in osteoporotic rats. Osteoporos Int 22:265–270

    Article  CAS  PubMed  Google Scholar 

  47. Viera-Negron YE, Ruan WH, Winger JN, Hou X, Sharawy MM, Borke JL (2008) Effect of ovariectomy and alendronate on implant osseointegration in rat maxillary bone. J Oral Implantol 34:76–82

    Article  PubMed  Google Scholar 

  48. Qi M, Hu J, Li J, Li J, Dong W, Feng X et al (2012) Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits. Bone 50:119–127

    Article  CAS  PubMed  Google Scholar 

  49. Tsetsenekou E, Papadopoulos T, Kalyvas D, Papaioannou N, Tangl S, Watzek G (2012) The influence of alendronate on osseointegration of nanotreated dental implants in New Zealand rabbits. Clin Oral Implants Res 23:659–666

    Article  PubMed  Google Scholar 

  50. Yildiz A, Esen E, Kurkcu M, Damlar I, Daglioglu K, Akova T (2010) Effect of zoledronic acid on osseointegration of titanium implants: an experimental study in an ovariectomized rabbit model. J Oral Maxillofac Surg 68:515–523

    Article  PubMed  Google Scholar 

  51. Gao Y, Zou S, Liu X, Bao C, Hu J (2009) The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats. Biomaterials 30:1790–1796

    Article  CAS  PubMed  Google Scholar 

  52. Peter B, Gauthier O, Laib S, Bujoli B, Guicheux J, Janvier P et al (2006) Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats. J Biomed Mater Res A 76:133–143

    Article  PubMed  CAS  Google Scholar 

  53. Stadelmann VA, Gauthier O, Terrier A, Bouler JM, Pioletti DP (2008) Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study. Eur Cell Mater 16:10–16

    Article  CAS  PubMed  Google Scholar 

  54. Bukata SV (2011) Systemic administration of pharmacological agents and bone repair: what can we expect. Injury 42(6):605–608

    Article  PubMed  Google Scholar 

  55. Rozental TD, Vazquez MA, Chacko AT, Ayogu N, Bouxsein ML (2009) Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg Am 34(4):595–602

    Article  PubMed  Google Scholar 

  56. Colon-Emeric C, Nordsletten L, Olson S, Major N, Boonen S, Haentjens P et al (2011) Association between timing of zoledronic acid infusion and hip fracture healing. Osteoporos Int 22(8):2329–2336

    Article  CAS  PubMed  Google Scholar 

  57. Adolphson P, Abbaszadegan H, Boden H, Salemyr M, Henriques T (2000) Clodronate increases mineralization of callus after Colles’ fracture: a randomized, double-blind, placebo-controlled, prospective trial in 32 patients. Acta Orthop Scand 71(2):195–200

    Article  CAS  PubMed  Google Scholar 

  58. van der Poest Clement E, Patka P, Vandormael K, Haarman H, Lips P (2000) The effect of alendronate on bone mass after distal forearm fracture. J Bone Miner Res 15(3):586–593

    Article  PubMed  Google Scholar 

  59. Koester MC, Spindler KP (2006) Pharmacologic agents in fracture healing. Clin Sports Med 25(1):63–73

    Article  PubMed  Google Scholar 

  60. Gong HS, Song CH, Lee YH, Rhee SH, Lee HJ, Baek GH (2012) Early initiation of bisphosphonate does not affect healing and outcomes of volar plate fixation of osteoporotic distal radial fractures. J Bone Joint Surg Am 94:1729–1736

    Article  PubMed  Google Scholar 

  61. Uchiyama S, Itsubo T, Nakamura K et al (2013) Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time. Bone Joint J 95-B(11):1544–1550

    Article  CAS  PubMed  Google Scholar 

  62. Lin T, Yan S-G, Cai X-Z, Ying Z-M (2012) Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials. Osteoporos Int 23:1823–1834

    Article  CAS  PubMed  Google Scholar 

  63. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357(18):1799–1809

    Article  CAS  PubMed  Google Scholar 

  64. Eriksen EF, Lyles KW, Colon-Emeric CS, Pieper CF, Magaziner JS, Adachi JD et al (2009) Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture. J Bone Miner Res 24(7):1308–1313

    Article  CAS  PubMed  Google Scholar 

  65. Kim TY, Ha YC, Kang BJ, Lee YK, Koo KH (2012) Does early administration of bisphosphonate affect fracture healing in patients with intertrochanteric fractures? J Bone Joint Surg (Br) 94-B:956–960

    Article  Google Scholar 

  66. McClung M, Harris ST, Miller PD et al (2013) Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126(1):13–20

    Article  CAS  PubMed  Google Scholar 

  67. Lewiecki EM (2010) Treatment of osteoporosis with denosumab. Maturitas 66(2):182–186

    Article  CAS  PubMed  Google Scholar 

  68. Moen MD, Keam SJ (2011) Denosumab: a review of its use in the treatment of postmenopausal osteoporosis. Drugs Aging 28(1):63–82

    Article  CAS  PubMed  Google Scholar 

  69. Gerstenfeld LC, Sacks DJ, Pelis M, Mason ZD, Graves DT, Barrero M et al (2009) Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res 24(2):196–208

    Article  CAS  PubMed  Google Scholar 

  70. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765

    Article  CAS  PubMed  Google Scholar 

  71. Adami S, Libanati C, Boonen S, Cummings SR, Ho PR, Wang A, Siris E, Lane JM et al (2012) Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial. J Bone Joint Surg Am 94:2113–2119

    Article  PubMed  Google Scholar 

  72. Huusko TM, Karppi P, Kautiainen H, Suominen H, Avikainen V, Sulkava R (2002) Randomized, double-blind, clinically controlled trial of intranasal calcitonin treatment in patients with hip fracture. Calcif Tissue Int 71(6):478–484

    Article  CAS  PubMed  Google Scholar 

  73. Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S et al (2000) A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 109(4):267–276

    Article  CAS  PubMed  Google Scholar 

  74. Lyritis G, Boscainos PJ (2001) Calcitonin effects on cartilage and fracture healing. J Musculoskelet Neuronal Interact 2(2):137–142

    CAS  PubMed  Google Scholar 

  75. Bulbul M, Esenyel CZ, Esenyel M, Ayanoglu S, Bilgic B, Gulmez T (2008) Effects of calcitonin on the biomechanics, histopathology, and radiography of callus formation in rats. J Orthop Sci 13(2):136–144

    Article  CAS  PubMed  Google Scholar 

  76. Lyritis GP, Tsakalakos N, Magiasis B, Karachalios T, Yiatzides A, Tsekoura M (1991) Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study. Calcif Tissue Int 49(6):369–372

    Article  CAS  PubMed  Google Scholar 

  77. Lyritis GP, Paspati I, Karachalios T, Ioakimidis D, Skarantavos G, Lyritis PG (1997) Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study. Acta Orthop Scand Suppl 275:112–114

    Article  CAS  PubMed  Google Scholar 

  78. Migliaccio S, Brama M, Spera G (2007) The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis. Clin Interv Aging 2(1):55–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Barrett-Connor E, Grady D, Sashegyi A, Anderson PW, Cox DA, Hoszowski K et al (2002) Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 287(7):847–857

    Article  CAS  PubMed  Google Scholar 

  80. Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ et al (1995) The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 332(24):1589–1593

    Article  CAS  PubMed  Google Scholar 

  81. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333

    Article  CAS  PubMed  Google Scholar 

  82. Sahiner T, Aktan E, Kaleli B, Oguzhanoglu A (1998) The effects of postmenopausal hormone replacement therapy on sympathetic skin response. Maturitas 30(1):85–88

    Article  CAS  PubMed  Google Scholar 

  83. Taranta A, Brama M, Teti A, De luca V, Scandurra R, Spera G et al (2002) The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 30(2):368–376

    Article  CAS  PubMed  Google Scholar 

  84. Ensrud KE, Stock JL, Barrett-Connor E, Grady D, Mosca L, Khaw KT et al (2008) Effects of raloxifene on fracture risk in postmenopausal women: the Raloxifene Use for the Heart Trial. J Bone Miner Res 23(1):112–120

    Article  CAS  PubMed  Google Scholar 

  85. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al (1999) 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. JAMA 282(7):637–645

    Article  CAS  PubMed  Google Scholar 

  86. Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M et al (2002) Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res 17(12):2237–2246

    Article  CAS  PubMed  Google Scholar 

  87. Stuermer EK, Sehmisch S, Rack T, Wenda E, Seidlova-Wuttke D, Tezval M et al (2010) Estrogen and raloxifene improve metaphyseal fracture healing in the early phase of osteoporosis. A new fracture-healing model at the tibia in rat. Langenbeck’s Arch Surg 395(2):163–172

    Article  CAS  Google Scholar 

  88. Beil FT, Barvencik F, Gebauer M, Seitz S, Rueger JM, Ignatius A et al (2010) Effects of estrogen on fracture healing in mice. J Trauma 69(5):1259–1265

    Article  CAS  PubMed  Google Scholar 

  89. Spiro AS, Khadem S, Jeschke A, Marshall RP, Pogoda P, Ignatius A, Amling M, Beil FT (2013) The SERM raloxifene improves diaphyseal fracture healing in mice. J Bone Miner Metab 31:629–636

    Article  CAS  PubMed  Google Scholar 

  90. Sibai T, Morgan EF, Einhorn TA (2011) Anabolic agents and bone quality. Clin Orthop Relat Res 469(8):2215–2224

    Article  PubMed  Google Scholar 

  91. Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136(8):3632–3638

    Article  CAS  PubMed  Google Scholar 

  92. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21(2):115–137

    CAS  PubMed  Google Scholar 

  93. Friedl G, Turner RT, Evans GL, Dobnig H (2007) Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism. J Orthop Res 25(11):1454–1464

    Article  CAS  PubMed  Google Scholar 

  94. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344(19):1434–1441

    Article  CAS  PubMed  Google Scholar 

  95. Andreassen TT, Ejersted C, Oxlund H (1999) Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14(6):960–968

    Article  CAS  PubMed  Google Scholar 

  96. Andreassen TT, Willick GE, Morley P, Whitfield JF (2004) Treatment with parathyroid hormone hPTH(1-34), hPTH(1-31), and monocyclic hPTH(1-31) enhances fracture strength and callus amount after withdrawal fracture strength and callus mechanical quality continue to increase. Calcif Tissue Int 74(4):351–356

    Article  CAS  PubMed  Google Scholar 

  97. Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH et al (2005) Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am 87(4):731–741

    PubMed  Google Scholar 

  98. Manabe T, Mori S, Mashiba T, Kaji Y, Iwata K, Komatsubara S et al (2007) Human parathyroid hormone (1-34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 40(6):1475–1482

    Article  CAS  PubMed  Google Scholar 

  99. Komatsubara S, Mori S, Mashiba T, Nonaka K, Seki A, Akiyama T et al (2005) Human parathyroid hormone (1-34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora. Bone 36(4):678–687

    Article  CAS  PubMed  Google Scholar 

  100. Kakar S, Einhorn TA, Vora S, Miara LJ, Hon G, Wigner NA et al (2007) Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures. J Bone Miner Res 22(12):1903–1912

    Article  CAS  PubMed  Google Scholar 

  101. Nakajima A, Shimoji N, Shiomi K, Shimizu S, Moriya H, Einhorn TA et al (2002) Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1-34). J Bone Miner Res 17(11):2038–2047

    Article  CAS  PubMed  Google Scholar 

  102. Nakazawa T, Nakajima A, Shiomi K, Moriya H, Einhorn TA, Yamazaki M (2005) Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1-34) on chondrogenesis in a model of experimental fracture healing. Bone 37(5):711–719

    Article  CAS  PubMed  Google Scholar 

  103. Jorgensen NR, Schwarz P (2011) Effects of anti-osteoporosis medications on fracture healing. Curr Osteoporos Rep 9(3):149–155

    Article  PubMed  Google Scholar 

  104. Reynolds DG, Shaikh S, Papuga MO, Lerner AL, O’Keefe RJ, Schwarz EM et al (2009) muCT-based measurement of cortical bone graft-to-host union. J Bone Miner Res 24(5):899–907

    Article  PubMed  Google Scholar 

  105. Rubery PT, Bukata SV (2010) Teriparatide may accelerate healing in delayed unions of type III odontoid fractures: a report of 3 cases. J Spinal Disord Tech 23(2):151–155

    Article  PubMed  Google Scholar 

  106. Bukata SV, Puzas JE (2010) Orthopedic uses of teriparatide. Curr Osteoporos Rep 8(1):28–33

    Article  PubMed  Google Scholar 

  107. Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K et al (2010) Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 25(2):404–414

    Article  CAS  PubMed  Google Scholar 

  108. Aspenberg P, Johansson T (2010) Teriparatide improves early callus formation in distal radial fractures. Acta Orthop 81(2):234–236

    Article  PubMed  PubMed Central  Google Scholar 

  109. Peichl P, Holzer LA, Maier R, Holzer G (2011) Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am 93(17):1583–1587

    Article  PubMed  Google Scholar 

  110. Ohtori S, Inoue G, Orita S et al (2012) Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis. Spine 37(23):E1464–E1468

    Article  PubMed  Google Scholar 

  111. Ohtori S, Inoue G, Orita S et al (2013) Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective. Spine 38(8):E487–E492

    Article  PubMed  Google Scholar 

  112. Schilcher J, Sandberg O, Isaksson H, Aspenberg P (2014) Histology of 8 atypical femoral fractures: remodeling but no healing. Acta Orthop 85(3):280–286

    Article  PubMed  PubMed Central  Google Scholar 

  113. Chiang CY, Zebaze RM, Ghasem-Zadeh A et al (2013) Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone 52(1):360–365

    Article  CAS  PubMed  Google Scholar 

  114. Miyakoshi N, Aizawa T, Shimada Y et al (2015) Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide. J Bone Miner Metab 33:553–559

    Article  CAS  PubMed  Google Scholar 

  115. Kim KM, Park W, Oh SY et al (2014) Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw. Osteoporos Int 25(5):1625–1632

    Article  CAS  PubMed  Google Scholar 

  116. Habermann B, Kafchitsas K, Olender G, Augat P, Kurth A (2010) Strontium ranelate enhances callus strength more than PTH 1-34 in an osteoporotic rat model of fracture healing. Calcif Tissue Int 86(1):82–89

    Article  CAS  PubMed  Google Scholar 

  117. Arlot ME, Jiang Y, Genant HK, Zhao J, Burt-Pichat B, Roux JP et al (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23(2):215–222

    Article  CAS  PubMed  Google Scholar 

  118. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350(5):459–468

    Article  CAS  PubMed  Google Scholar 

  119. Reginster JY, Felsenberg D, Boonen S, Diez-Perez A, Rizzoli R, Brandi ML et al (2008) Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum 58(6):1687–1695

    Article  CAS  PubMed  Google Scholar 

  120. Cebesoy O, Tutar E, Kose KC, Baltaci Y, Bagci C (2007) Effect of strontium ranelate on fracture healing in rat tibia. Joint Bone Spine 74(6):590–593

    Article  PubMed  Google Scholar 

  121. Li YF, Luo E, Feng G, Zhu SS, Li JH, Hu J (2010) Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats. Osteoporos Int 21(11):1889–1897

    Article  CAS  PubMed  Google Scholar 

  122. Ozturan KE, Demir B, Yucel I, Cakici H, Yilmaz F, Haberal A (2011) Effect of strontium ranelate on fracture healing in the osteoporotic rats. J Orthop Res 29(1):138–142

    Article  CAS  PubMed  Google Scholar 

  123. Alegre DN, Ribeiro C, Sousa C, Correia J, Silva L, de Almeida L (2012) Possible benefits of strontium ranelate in complicated long bone fractures. Rheumatol Int 32(2):439–443

    Article  PubMed  Google Scholar 

  124. Tarantino U, Celi M, Saturnino L, Scialdoni A, Cerocchi I (2010) Strontium ranelate and bone healing: report of two cases. Clin Case Miner Bone Metab 7(1):65–68

    Google Scholar 

  125. ClinicalTrials.gov. National Institutes of Health (2015) Web https://clinicaltrials.gov/ct2/home

  126. EU Clinical Trials Register. European Medicines Agency (2015) Web. https://www.clinicaltrialsregister.eu/ctr-search/search

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Hegde, V., Jo, J.E., Andreopoulou, P. et al. Effect of osteoporosis medications on fracture healing. Osteoporos Int 27, 861–871 (2016). https://doi.org/10.1007/s00198-015-3331-7

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