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Year : 2014  |  Volume : 6  |  Issue : 4  |  Page : 221  

Bisphosphonates and direct fracture healing: Area to be explored

1 Department of Orthopedics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Dentistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Web Publication16-Oct-2014

Correspondence Address:
Lata Goyal
Department of Dentistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand,
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Source of Support: None, Conflict of Interest: None

PMID: 25400402

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How to cite this article:
Goyal T, Goyal L. Bisphosphonates and direct fracture healing: Area to be explored. J Pharm Bioall Sci 2014;6:221

How to cite this URL:
Goyal T, Goyal L. Bisphosphonates and direct fracture healing: Area to be explored. J Pharm Bioall Sci [serial online] 2014 [cited 2022 Aug 12];6:221. Available from:

Bisphosphonates (BPs) are widely used antiresorptive agents in the treatment of osteoporosis. They act primarily through inactivation of osteoclasts. Since the activities of osteoblasts and osteoclasts are coupled, the use of BPs is associated with delayed bone remodelling due to reduction of both osteoblastic and osteoclastic activities. Many patients sustaining osteoporotic fractures will be receiving bisphosphonates and others will be started on this treatment for secondary prevention. The question remains that if BPs delays fracture healing or remodelling, should they be delayed till the fracture union has been achieved.

Fracture healing occurs by two mechanisms, direct and indirect. Maximum osteoclastic activity occurs about 6 weeks after the indirect bone healing starts although low grade osteoclastic activity can be seen early in the fracture healing. [1] This is in contrast to direct bone healing where the osteoclasts come into play in early stages. The use of bisphosphonates in indirect bone healing is associated with increased ratio of woven to lamellar bone and increased bulk of callus. Increased volume and mineral content of callus may not confer mechanical advantage and the callus formed appears to be of inferior quality callus resulting in reduced strength to failure. [2] It has been shown in experimental models that use of BP during the first week of fracture healing did not impair indirect bone healing, but this impairment was seen if the drug was continued for a longer time. [3],[4] Thus, cessation of BP before the peaking of osteoclastic activity in indirect fracture healing can be protective against the deleterious effects on indirect fracture healing.

Savaridas et al. [5] in an animal model studied the effect of Ibandronate (1 μg/kg) on rigid compression plate fixation of tibial osteotomy (direct bone healing model). Compared to a control group, the rodent model receiving BPs had poorer radiological, biomechanical and histological evidence of fracture healing. They concluded that in therapeutic doses BPs has an inhibitory effect on direct fracture healing. This is the only article that studied the role of BP in a direct bone healing model. Though a large number of patients are receiving BP during the fracture healing, there are no human studies at present studying in vivo effect of BP therapy on the bone healing.

Though bisphosphonates is an important drug in osteoporosis, but timing of its administration may need to be tailored in the healing phase of the fracture. In vivo studies are needed on the effect of bisphosphonates on histological rather than radiological fracture healing.

   References Top

Schell H, Lienau J, Epari DR, Seebeck P, Exner C, Muchow S, et al. Osteoclastic activity begins early and increases over the course of bone healing. Bone 2006;38:547-54.  Back to cited text no. 1
Li J, Mori S, Kaji Y, Mashiba T, Kawanishi J, Norimatsu H. Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats. J Bone Miner Res 1999;14:969-79.  Back to cited text no. 2
McDonald MM, Dulai S, Godfrey C, Amanat N, Sztynda T, Little DG. Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling. Bone 2008;43:653-62.  Back to cited text no. 3
Deckers MM, Van Beek ER, Van Der Pluijm G, Wetterwald A, Van Der Wee-Pals L, Cecchini MG, et al. Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice. J Bone Miner Res 2002;17:998-1007.  Back to cited text no. 4
Savaridas T, Wallace RJ, Salter DM, Simpson AH. Do bisphosphonates inhibit direct fracture healing? A laboratory investigation using an animal model. Bone Joint J 2013;95-B:1263-8.  Back to cited text no. 5


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