How do bisphosphonates affect fracture healing?

Abstract

Bisphosphonates (BPs) have been in use for many years for the treatment of osteoporosis, multiple myeloma, Paget's disease, as well as a variety of other diseases in which there is reduced bone mineral density. Given that bisphosphonates inhibit bone resorption, an important stage of fracture healing; this class of compounds has been widely studied in preclinical models regarding their influence on fracture healing. In animal models, bisphosphonate treatment is associated with a larger fracture callus, coincident with a delay in remodeling from primary woven bone to lamellar bone, but there is no delay in formation of the fracture callus. In humans, de novo use of bisphosphonate therapy after fracture does not appear to have a significant effect on fracture healing. Rarely, patients with long term use of Bisphosphonates may develop an atypical fracture and delay in fracture healing has been observed. In summary, bisphosphonates appear safe for use in the setting of acute fracture management in the upper and lower extremity in humans. While much remains unknown about the effects on healing of long-term bisphosphonates, use prior to “typical” fracture, in the special case of atypical fracture, evidence suggests that bisphosphonates negatively influence healing.

Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

“…Another group of drugs used prior to the development of denosumab for both primary and secondary osteoporosis was bisphosphonates. Bisphosphonates are concentrated directly in bone and can enter the osteoclast where it causes an acidic medium in lacunae after activation [31]. Once internalized, they are toxic for the osteoclast.…”

“…They either inactivate or trigger apoptosis of the osteoclast depending on whether they are nitrogenous or non-nitrogenous bisphosphonates. They either cause apoptosis directly or inhibit the enzyme farnesyl pyrophosphate synthase [31].…”

A Review on Glucocorticoids Induced Osteoporosis: Pathogenesis, Diagnosis and Management by Some Natural Plants

“…pamidronate, alendronate, ibandronate, risedronate and zoledronate). All BPs have a high affinity for calcium and in the body they concentrate in the skeleton at sites of active bone remodeling preventing fractures in osteoporotic patients and reduce the risk of fracture by up to 50% [38,39] .…”

Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study

“…The common notion that atypical fractures are associated with a high risk of perioperative complications and a higher risk of delayed healing or non-union as well as consequential reoperations might have reinforced those fears [3][4][5][6][7][8]. The perception of a poor healing capacity is based on case reports [9,10] and case series [5,6,[11][12][13], which contrast results from animal and human studies showing no negative impact of bisphosphonates on fracture healing, except for callus remodeling [14,15]. In long-term bisphosphonate exposure, the severe suppression of bone turnover has been suggested to decrease the anabolic response of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00198-019-05249-3) contains supplementary material, which is available to authorized users.…”