Atypical subtrochanteric femoral shaft fractures: role for mechanics and bone quality

Abstract

Bisphosphonates are highly effective agents for reducing osteoporotic fractures in women and men, decreasing fracture incidence at the hip and spine up to 50%. In a small subset of patients, however, these agents have recently been associated with 'atypical femoral fractures' (AFFs) in the subtrochanteric region or the diaphysis. These fractures have several atypical characteristics, including occurrence with minimal trauma; younger age than typical osteoporotic fractures; occurrence at cortical, rather than cancellous sites; early radiographic appearance similar to that of a stress fracture; transverse fracture pattern rather than the familiar spiral or transverse-oblique morphologies; initiation on the lateral cortex; and high risk of fracture on the contralateral side, at the same location as the initial fracture. Fracture is a mechanical phenomenon that occurs when the loads applied to a structure such as a long bone exceed its load-bearing capacity, either due to a single catastrophic overload (traumatic failure) or as a result of accumulated damage and crack propagation at sub-failure loads (fatigue failure). The association of AFFs with no or minimal trauma suggests a fatigue-based mechanism that depends on cortical cross-sectional geometry and tissue material properties. In the case of AFFs, bisphosphonate treatment may alter cortical tissue properties, as these agents are known to alter bone remodeling. This review discusses the use of bisphosphonates, their effects on bone remodeling, mechanics and tissue composition, their significance as an effective therapy for osteoporosis, and why these agents may increase fracture risk in a small population of patients.

�Atypical� atypical femur fractures and use of bisphosphonates

“…Additionally, bisphosphonates accumulate at sites of high bone remodeling including sites of stress fractures. This could affect the intracortical repair of a developing stress fracture and ultimately lead to a complete fracture (5,6,11,15). We present a patient with unusual spontaneous periosteal reactions of both medial femora.…”

Tibial stress reaction presenting as bilateral shin pain in a man taking denosumab for giant cell tumor of the bone

“…Typical of patients receiving denosumab therapy, our patient had a significantly decreased fasting urinary N-terminal telopeptide level, compatible with suppressed bone turnover. Suppression of bone turnover may affect bone mineralization, bone quality, formation of the collagen network, and increase the microfracture burden, and this has been suggested as a possible mechanism for predisposition for atypical fractures, although the data in regards to this hypothesis has been inconclusive [5,25].…”

Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

“…3 Long-term studies with bisphosphonate have shown persistent antifracture efficacy and much larger increases in BMD at sites where trabecular bone is abundant (vertebral bone) compared with those where cortical bone is prevalent (femoral neck, total hipy). 1 Cortical bone has a lower surface-to-bone marrow ratio, and as bone turnover is a surface-based mechanism cortical bone is considered to have lower levels of bone turnover.…”

“…1 However, concerns emerged during recent years that longer bone turnover reduction might favor the occurrence of fatigue fractures [2][3][4] (fractures that result from repetitive normal loading and not from a singular overloading). Increasing numbers of patients with fatigue fractures after antiresorptive therapy, in particular after long-term bisphosphonate treatment, have been reported.…”