Seminars in Arthritis and Rheumatism

Objectives: Bisphosphonate-associated atypical sub-rrochanteric femur fractures {ASFF) may be seen with long-term bisphosphonate use, though these fractures are also seen in patients never exposed to bisphosphonates. One theoiy for the mechanism of action whereby bisphosphonates may induce these ASFF is over-suppression of bone turnover. Bisphosphonates suppress bone turnover. but in bisphosphonate clinical trials. over-suppression defined whether by maintaining the biochemical markers of bone turnover below the defined reference range or by quantitative bone histomorphomeny, has not been observed. Mec/1ods: We studied 15 clinic patients referred to The Colorado Cen.ter for Bone Research (CCBR) after they had a bisphosphonate-associated ASFF and performed quantitative bone histomorphometry both before and after 12 months of teriparatide (20 μg SQ/day). All patients had been on long-term alendronate (mean = 7 years. range: 6--11 years) and had already had intramedullary rods placed when first seen (6 weeks co 7 months after rod placement). Alendronatc had been discontinued in all patients at the time of their first clinic visit to CCBR. All of the fractures fulfilled The American· Society for Bone and Mineral Research major radiological criteria for ASFF. Results: Three key dy11a1nic histomorphometric features show that 7 of the 15 patients had unmeasurable bone fonnation, mineralizing surface, and mineral apposition. while the other 8 patients had measurable dynamic parameters; although for all 15 patients, the mean vc1lues for all 3 dynamic parameters was far below the average for the published normal population. Administration of teriparatide was associated with an increase in all 3 dynamic hisromorphometric parameters. Baseline bone turnover markers did not correlate with the baseline histomorphometry. While there is heterogeneity in the bone turnover in patients with bisphosphonate ASFF, there is a large portion in this uncontrolled series that had absent bone turnover at the standard biopsy site (iliac crest). Discontinuation of the bisphosphon.ate and .administration of the anabolic agenr, tcriparatide was c1ssoci.ated with improvement in bone turnover. Conclusions: While our srudy does nor esrablish causality or address the ability of teriparatide to prevent progi:ession of early stress fracture to displaced fractures, it does suggest that teriparatide may improve bone formation in these patients. Our study should stimulate other invesrigations using larger sample sizes and early stre_ss fractures to see if anabolic agents can reverse these fractures from becoming displaced.