Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw

Abstract

In recent years, atypical femoral fractures and osteonecrosis of the jaw have emerged as potential complications of long-term bisphosphonate therapy; osteonecrosis of the jaw has also been reported in patients receiving high doses of denosumab. The pathophysiology of both conditions is poorly defined, and the underlying mechanisms are likely to differ. The initiation of atypical fractures in the lateral femoral shaft suggests that reduced tensile strength, possibly secondary to alterations in the material properties of bone resulting from low bone turnover, may be an important pathogenetic factor. Osteonecrosis of the jaw is characterised by infection, inflammation, bone resorption and bone necrosis, but the sequence in which these occur has not been established. However, the observation that bone resorption occurs in close proximity to microbial structures suggests that infection may be the most important trigger, often as a result of dental disease. Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa.

Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration

“…However, long-term BP treatment is associated with adverse events, including atypical fractures of the femoral diaphysis (AFF) and osteonecrosis of the jaw. 2 Epidemiological data indicate that AFF account for less than 1% of all hip and femoral fractures. 2,3 Characteristic features of AFF include their unique radiological features, long-term prodromal pain, occurrence after minimal or no trauma, bilaterality and delayed healing.…”

“…2 Epidemiological data indicate that AFF account for less than 1% of all hip and femoral fractures. 2,3 Characteristic features of AFF include their unique radiological features, long-term prodromal pain, occurrence after minimal or no trauma, bilaterality and delayed healing. 3 Although the causal association between long-term BP use and AFF is still debated, the most likely mechanisms relate to the suppression of bone turnover leading to attenuation of bone material properties, including increase in density and homogeneisity of mineralization, collagen maturity, microcrack accumulation, propagation and impaired Empirical management for AFF includes application of intramedullary full-length nails, discontinuation of BPs, supplementation with calcium and vitamin D and anabolic therapy with teriparatide (TRP) or strontium ranelate (SR).…”

Bisphosphonate therapy for osteoporosis: The long and short of it

“…Some studies have linked these two rare adverse events to length of therapy. (2)(3)(4) The long residence time in bone of bisphosphonates, along with possible time-related adverse events, have led to the concept of a drug holiday. The drug holiday is a period of time, after continuous bisphosphonate therapy, when treatment is stopped.…”

An atypical fracture in male patient with osteogenesis imperfecta

“…In recent years, a series of secondary effects related with their prolonged use have been reported, among which is the possible development of so-called atypical fractures, whose location and radiological appearance differ from classical fractures with an osteoporotic profile (2). Although a number of questions remains, the essential underlying physiopathology appears to be the marked and sustained suppression of bone remodelling which this group of drugs may generate, with alterations in mineralisation and the accumulation of micro-fractures which may trigger a reduction in bone strength (3). In addition, bisphosphonates inhibit vascular proliferation and also induce apoptosis in endothelial cells, which may contribute to a reduction of bone regeneration capacity (4).…”