Bone Abstracts

Impaired bone material properties have been invoked as being responsible for the development of atypical femoral fractures (AFF) after long term bisphosphonate use. We therefore analyzed bone material properties in a bone biopsy obtained at the fracture site from an 88-year-old female with AFF, who had been treated with alendronate for 8 years. We used conventional histology, quantitative backscattered electron imaging (qBEI), and Raman spectroscopy (RS).

Histology revealed numerous eroded surfaces, widened osteoid seams, and osteocytic osteolysis. qBEI exhibited a scaffold of highly mineralized, porous bone matrix with numerous enlarged, osteocyte lacunae. Bone mineralization density distribution (BMDD) was shifted towards lower and more heterogenous mineralization compared to a normal reference database: mean calcium content (CaMean −4.1% and CaPeak −1.8%), mineralization heterogeneity (CaWidth +29.3%), bone with reduced mineralization (CaLow +111%) and bone with increased mineralization (CaHigh −2%). RS data obtained at open osteons were compared with iliac crest biopsies from 35 healthy premenopausal, 16 treatment-naive osteoporotic women (PMC) and osteoporotic females (OP) treated with different bisphosphonates. The mineral/matrix ratio of AFF bone was similar to two alendronate and two risedronate groups, lower than PMC, and higher than either OP or OP-zoledronate groups. The proteoglycan content was higher in the AFF biopsy compared to all other groups. The mineral crystallinity of AFF bone was similar to both ALN groups, but higher compared to all other groups. Most significantly, however, we detected increased levels of pyrophosphate at osteoid/mineralized bone interfaces in AFF bone, a feature absent in other biopsies obtained from subjects after long term bisphosphonate treatment.

In conclusion, bone from this case of AFF showed several abnormalities: i) altered arrangement of osteons ii) impaired mineralization and iii) Appreciable pyrophosphate accumulation, which might cause the impaired mineralization. Taken together, these changes may be responsible for the focally reduced bone strength in AFF.