The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies

Schindeler, 2008, Bone remodeling during fracture repair: the cellular picture, Semin. Cell Dev. Biol., 19, 459, 10.1016/j.semcdb.2008.07.004 Tsiridis, 2007, Molecular aspects of fracture healing: which are the important molecules?, Injury, 38, S11, 10.1016/j.injury.2007.02.006 Marsell, 2011, The biology of fracture healing, Injury, 42, 551, 10.1016/j.injury.2011.03.031 Giannoudis, 2007, Fracture healing: the diamond concept, Injury, 38, S3, 10.1016/S0020-1383(08)70003-2 Copuroglu, 2013, Fracture non-union: who is at risk?, Injury, 44, 1379, 10.1016/j.injury.2013.08.003 Giannoudis, 2007, Fracture healing in osteoporotic fractures: is it really different? A basic science perspective, Injury, 38, S90, 10.1016/j.injury.2007.02.014 Kanis, 2019, European guidance for the diagnosis and management of osteoporosis in postmenopausal women, Osteoporos. Int., 30, 3, 10.1007/s00198-018-4704-5 Yaacobi, 2017, Surgical treatment of osteoporotic fractures: an update on the principles of management, Injury, 48, S34, 10.1016/j.injury.2017.08.036 He, 2011, Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: a drill-hole defect model, Bone, 48, 1388, 10.1016/j.bone.2011.03.720 Histing, 2013, Delayed fracture healing in aged senescence-accelerated P6 mice, J. Investig. Surg., 26, 30, 10.3109/08941939.2012.687435 Hao, 2007, Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats, Bone, 41, 631, 10.1016/j.bone.2007.06.006 Oliver, 2013, Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats, Osteoporos. Int., 24, 2581, 10.1007/s00198-013-2345-2 Namkung-Matthai, 2001, Osteoporosis influences the early period of fracture healing in a rat osteoporotic model, Bone, 28, 80, 10.1016/S8756-3282(00)00414-2 Cao, 2018, Strontium ranelate combined with insulin is as beneficial as insulin alone in treatment of fracture healing in ovariectomized diabetic rats, Med. Sci. Monit., 24, 6525, 10.12659/MSM.911573 Kubo, 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, 197, 10.1016/S0960-0760(99)00032-1 McCann, 2008, Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model, J. Orthop. Res., 26, 384, 10.1002/jor.20505 Xu, 2003, Early period of fracture healing in ovariectomized rats, Chin. J. Traumatol., 6, 160 Wong, 2019, A metaphyseal fracture rat model for mechanistic studies of osteoporotic bone healing, Eur. Cells Mater., 37, 420, 10.22203/eCM.v037a25 Guo, 2017, Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats, PLoS ONE, 12, 10.1371/journal.pone.0187683 Wang, 2005, Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model, Chin. J. Traumatol., 8, 111 Thormann, 2014, Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats, Injury, 45, 487, 10.1016/j.injury.2013.10.033 Habermann, 2010, Strontium ranelate enhances callus strength more than PTH 1–34 in an osteoporotic rat model of fracture healing, Calcif. Tissue Int., 86, 82, 10.1007/s00223-009-9317-8 Kido, 2014, Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats, Aging Clin. Exp. Res., 26, 473, 10.1007/s40520-014-0199-x Tatehara, 2011, Osteoporosis influences the early period of the healing after distraction osteogenesis in a rat osteoporotic model, J. Cranio-Maxillofac. Surg., 39, 2, 10.1016/j.jcms.2010.03.001 Cao, 2002, Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res., 17, 2237, 10.1359/jbmr.2002.17.12.2237 Lill, 2003, Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis, J. Orthop. Res., 21, 836, 10.1016/S0736-0266(02)00266-8 Zura, 2017, Bone fracture nonunion rate decreases with increasing age: a prospective inception cohort study, Bone, 95, 26, 10.1016/j.bone.2016.11.006 Zura, 2016, Epidemiology of fracture nonunion in 18 human bones, JAMA Surg., 151, 10.1001/jamasurg.2016.2775 van Wunnik, 2011, Osteoporosis is not a risk factor for the development of nonunion: a cohort nested case-control study, Injury, 42, 1491, 10.1016/j.injury.2011.08.019 Nikolaou, 2009, The influence of osteoporosis in femoral fracture healing time, Injury, 40, 663, 10.1016/j.injury.2008.10.035 Gorter, 2020, Does osteoporosis affect the healing of subcapital humerus and distal radius fractures?, J. Orthop., 22, 237, 10.1016/j.jor.2020.05.004 Murphy, 2015, PTH(1–34) treatment increases bisphosphonate turnover in fracture repair in rats, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res., 30, 1022, 10.1002/jbmr.2424 McDonald, 2008, Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling, Bone, 43, 653, 10.1016/j.bone.2008.05.019 Aydogan, 2016, The effect of vitamin D and bisphosphonate on fracture healing: an experimental study, J. Clin. Orthop. Trauma, 7, 90, 10.1016/j.jcot.2016.01.003 Gerstenfeld, 2009, Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 24, 196, 10.1359/jbmr.081113 Amanat, 2008, The effect of zoledronic acid on the intrinsic material properties of healing bone: an indentation study, Med. Eng. Phys., 30, 843, 10.1016/j.medengphy.2007.09.008 Baima Filho, 2020, The analysis of alendronate action in bone fracture healing in rats, J. Clin. Orthop. Trauma, 11, S856, 10.1016/j.jcot.2020.07.027 Leiblein, 2020, Do antiosteoporotic drugs improve bone regeneration in vivo?, Eur. J. Trauma Emerg. Surg., 46, 287, 10.1007/s00068-019-01144-y Menzdorf, 2016, Local pamidronate influences fracture healing in a rodent femur fracture model: an experimental study, BMC Musculoskelet. Disord., 17, 255, 10.1186/s12891-016-1113-9 Turker, 2016, Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model, Joint Dis. Rel. Surg., 27, 9 Hao, 2015, Zoledronic acid suppresses callus remodeling but enhances callus strength in an osteoporotic rat model of fracture healing, Bone, 81, 702, 10.1016/j.bone.2015.09.018 Hauser, 2018, Healing of fractures in osteoporotic bones in mice treated with bisphosphonates - a transcriptome analysis, Bone, 112, 107, 10.1016/j.bone.2018.04.017 Kolios, 2010, Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?, Calcif. Tissue Int., 86, 23, 10.1007/s00223-009-9318-7 Spiro, 2013, The SERM raloxifene improves diaphyseal fracture healing in mice, J. Bone Miner. Metab., 31, 629, 10.1007/s00774-013-0461-x Ramalho-Ferreira, 2015, Raloxifene enhances peri-implant bone healing in osteoporotic rats, Int. J. Oral Maxillofac. Surg., 44, 798, 10.1016/j.ijom.2015.02.018 Stuermer, 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, 163, 10.1007/s00423-008-0436-x Ulrich-Vinther, 2005, Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength, Calcif. Tissue Int., 76, 280, 10.1007/s00223-004-0126-9 Flick, 2003, Effects of receptor activator of NFkappaB (RANK) signaling blockade on fracture healing, J. Orthop. Res., 21, 676, 10.1016/S0736-0266(03)00011-1 Lanske, 2019, Abaloparatide, a PTH receptor agonist with homology to PTHrP, enhances callus bridging and biomechanical properties in rats with femoral fracture, J. Orthop. Res., 37, 812, 10.1002/jor.24254 Milstrey, 2017, Dose-dependent effect of parathyroid hormone on fracture healing and bone formation in mice, J. Surg. Res., 220, 327, 10.1016/j.jss.2017.07.019 Tagil, 2010, Intermittent PTH(1–34) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures, Bone, 46, 852, 10.1016/j.bone.2009.11.009 Bernhardsson, 2018, Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse models, Acta Orthop., 89, 674, 10.1080/17453674.2018.1523771 Alder, 2020, Systemic parathyroid hormone enhances fracture healing in multiple murine models of type 2 diabetes mellitus, JBMR Plus, 4, 1, 10.1002/jbm4.10359 Chen, 2003, Combination of local and systemic parathyroid hormone enhances bone regeneration, Clin. Orthop. Relat. Res., 416, 291, 10.1097/01.blo.0000079443.64912.18 Lin, 2012, Prevention of atrophic nonunion by the systemic administration of parathyroid hormone (PTH 1–34) in an experimental animal model, J. Orthop. Trauma, 26, 719, 10.1097/BOT.0b013e31826f5b9e Alkhiary, 2005, Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1–34), J. Bone Joint Surg., 87, 731 Nozaka, 2008, Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats, Bone, 42, 90, 10.1016/j.bone.2007.08.041 Ellegaard, 2013, The effect of PTH(1–34) on fracture healing during different loading conditions, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res., 28, 2145, 10.1002/jbmr.1957 Kim, 1999, Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats, Iowa Orthop. J., 19, 71 Lin, 2020, Combined antisclerostin antibody and parathyroid hormone (1–34) synergistically enhance the healing of bone defects in ovariectomized rats, Z. Gerontol. Geriatr., 53, 163, 10.1007/s00391-019-01685-2 Tao, 2016, Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats, Z. Gerontol. Geriatr., 49, 423, 10.1007/s00391-015-0949-1 Tsuchie, 2013, Intermittent administration of human parathyroid hormone before osteosynthesis stimulates cancellous bone union in ovariectomized rats, Tohoku J. Exp. Med., 229, 19, 10.1620/tjem.229.19 Liu, 2017, Parathyroid hormone (1–34) promotes fracture healing in ovariectomized rats with type 2 diabetes mellitus, Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 28, 3043, 10.1007/s00198-017-4148-3 Tao, 2016, Combined treatment with parathyroid hormone (1–34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model, Med. Biol. Eng. Comput., 54, 1353, 10.1007/s11517-015-1402-8 Tao, 2019, Single-dose local administration of parathyroid hormone (1–34, PTH) with beta-tricalcium phosphate/collagen (beta-TCP/COL) enhances bone defect healing in ovariectomized rats, J. Bone Miner. Metab., 37, 28, 10.1007/s00774-018-0906-3 Kitaguchi, 2020, The combined effects of teriparatide and anti-RANKL monoclonal antibody on bone defect regeneration in ovariectomized mice, Bone, 130 Bruel, 2011, Strontium is incorporated into the fracture callus but does not influence the mechanical strength of healing rat fractures, Calcif. Tissue Int., 88, 142, 10.1007/s00223-010-9439-z Cebesoy, 2007, Effect of strontium ranelate on fracture healing in rat tibia, Joint Bone Spine, 74, 590, 10.1016/j.jbspin.2007.01.034 Li, 2010, Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats, Osteoporos. Int., 21, 1889, 10.1007/s00198-009-1140-6 Komrakova, 2015, The impact of strontium ranelate on metaphyseal bone healing in ovariectomized rats, Calcif. Tissue Int., 97, 391, 10.1007/s00223-015-0019-0 Ozturan, 2011, Effect of strontium ranelate on fracture healing in the osteoporotic rats, J. Orthop. Res., 29, 138, 10.1002/jor.21204 Li, 2014, Timing of the initiation of bisphosphonates after surgery for fracture healing: a systematic review and meta-analysis of randomized controlled trials, Osteoporos. Int., 26, 431, 10.1007/s00198-014-2903-2 Kim, 2012, Does early administration of bisphosphonate affect fracture healing in patients with intertrochanteric fractures?, J. Bone Joint Surg. Br., 94, 956, 10.1302/0301-620X.94B7.29079 Colon-Emeric, 2011, Association between timing of zoledronic acid infusion and hip fracture healing, Osteoporos. Int., 22, 2329, 10.1007/s00198-010-1473-1 van der Poest, 2000, The effect of alendronate on bone mass after distal forearm fracture, J. Bone Miner. Res., 15, 586, 10.1359/jbmr.2000.15.3.586 Uchiyama, 2013, Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time, Bone Joint J., 95-B, 1544, 10.1302/0301-620X.95B11.31652 Duckworth, 2019, Effect of alendronic acid on fracture healing: a multicenter randomized placebo-controlled trial, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res., 34, 1025, 10.1002/jbmr.3679 Gong, 2012, Early initiation of bisphosphonate does not affect healing and outcomes of volar plate fixation of osteoporotic distal radial fractures, J. Bone Joint Surg., 94, 1729, 10.2106/JBJS.K.01434 Hayer, 2017, Effect of zoledronic acid on fracture healing in osteoporotic patients with intertrochanteric fractures, Int. J. Appl. Basic Med. Res., 7, 48, 10.4103/2229-516X.198523 Lim, 2019, Effect of preoperative bisphosphonate treatment on fracture healing after internal fixation treatment of intertrochanteric femoral fractures, Hip Pelvis, 31, 75, 10.5371/hp.2019.31.2.75 Cho, 2015, Does the time of postoperative bisphosphonate administration affect the bone Union in Osteoporotic Intertrochanteric Fracture of Femur?, Hip & pelvis, 27, 258, 10.5371/hp.2015.27.4.258 Seo, 2016, Influence of early bisphosphonate administration for fracture healing in patients with osteoporotic proximal humerus fractures, Clin. Orthop. Surg., 8, 437, 10.4055/cios.2016.8.4.437 Shoji, 2018, The effect of bisphosphonates on the clinical and radiographic outcomes of distal radius fractures in women, J. Hand Surg., 43, 115, 10.1016/j.jhsa.2017.09.006 Solomon, 2009, The relation between bisphosphonate use and non-union of fractures of the humerus in older adults, Osteoporos. Int., 20, 895, 10.1007/s00198-008-0759-z Rozental, 2009, Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy, J. Hand Surg., 34, 595, 10.1016/j.jhsa.2008.12.011 Koshy, 2017, Effect of alendronate on the healing time of distal radial fractures treated conservatively: an observational study, Asian J. Pharm. Clin. Res., 10, 168, 10.22159/ajpcr.2017.v10i11.18156 Adami, 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, 10.2106/JBJS.K.00774 Han, 2020, The efficacy of teriparatide in improving fracture healing in hip fractures: a systematic review and meta-analysis, Biomed. Res. Int., 2020, 5914502, 10.1155/2020/5914502 Huang, 2016, Teriparatide improves fracture healing and early functional recovery in treatment of osteoporotic intertrochanteric fractures, Medicine (Baltimore), 95, 10.1097/MD.0000000000003626 Huang, 2015, Effect of teriparatide on unstable pertrochanteric fractures, Biomed. Res. Int., 2015 Kim, 2019, Short-term daily teriparatide improve postoperative functional outcome and fracture healing in unstable intertrochanteric fractures, Injury, 50, 1364, 10.1016/j.injury.2019.06.002 Kim, 2018, Does short-term weekly teriparatide improve healing in unstable intertrochanteric fractures?, J. Orthop. Surg. (Hong Kong), 26, 10.1177/2309499018802485 Bhandari, 2016, Does teriparatide improve femoral neck fracture healing: results from a randomized placebo-controlled trial, Clin. Orthop. Relat. Res., 474, 1234, 10.1007/s11999-015-4669-z Chesser, 2016, The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur: a randomised prospective mixed method pilot study, Bone Joint J., 98-B, 840, 10.1302/0301-620X.98B6.36794 Hong, 2019, The effectiveness and safety of parathyroid hormone in fracture healing: a meta-analysis, Clinics (Sao Paulo, Brazil), 74, 10.6061/clinics/2019/e800 Peichl, 2011, Parathyroid hormone 1–84 accelerates fracture-healing in pubic bones of elderly osteoporotic women, J. Bone Joint Surg., 93, 1583, 10.2106/JBJS.J.01379 Kanakaris, 2015, Enhancement of hip fracture healing in the elderly: evidence deriving from a pilot randomized trial, Injury, 46, 1425, 10.1016/j.injury.2015.06.033 Almirol, 2013, Effects of recombinant human parathyroid hormone on the anabolic window and lower extremity stress fracture healing in premenopausal women: a pilot study, J. Bone Miner. Res. Conf., 28 Aspenberg, 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, 404, 10.1359/jbmr.090731 Johansson, 2016, PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures. A randomized, controlled study of 40 patients, Acta Orthop., 87, 79, 10.3109/17453674.2015.1073050 Scaglione, 2016, Strontium ranelate as an adjuvant for fracture healing: clinical, radiological, and ultrasound findings in a randomized controlled study on wrist fractures, Osteoporos. Int., 27, 211, 10.1007/s00198-015-3266-z Yoon, 2020, Does teriparatide improve fracture Union?: A systematic review, J. Bone Metab., 27, 167, 10.11005/jbm.2020.27.3.167 Watts, 2017, Responses to treatment with teriparatide in patients with atypical femur fractures previously treated with bisphosphonates, J. Bone Miner. Res., 32, 1027, 10.1002/jbmr.3081 Greenspan, 2018, Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur, Osteopor. Int., 29, 501, 10.1007/s00198-017-4286-7 Yeh, 2017, Surgical outcome of atypical subtrochanteric and femoral fracture related to bisphosphonates use in osteoporotic patients with or without teriparatide treatment, BMC Musculoskelet. Disord., 18, 527, 10.1186/s12891-017-1878-5 Miyakoshi, 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, 10.1007/s00774-014-0617-3 Tsuchie, 2018, The effects of teriparatide on acceleration of bone healing following atypical femoral fracture: comparison between daily and weekly administration, Osteoporos. Int., 29, 2659, 10.1007/s00198-018-4658-7 Shin, 2019, A retrospective bicenter comparative study of surgical outcomes of atypical femoral fracture: Potential effect of teriparatide on fracture healing and callus formation, Bone, 128 Gong, 2012, Early initiation of bisphosphonate does notaffect healing and outcomes of volar plate fixation of osteoporotic distal radius fractures, Osteoporos. Int., S817