Quantitative Bone Histomorphometry in Patients with Bisphosphonate-Associated Atypical Subtrochanteric Femur Fractures Before and after 12 months of Teriparatide
Category: Osteoporosis - Treatment (Clinical)
Oral Presentations, Presentation Number: 1030
Session: Concurrent Oral Session 05: John H. Carsten's Memorial Session for Osteoporosis Treatment
Saturday, October 13, 2012 10:45 AM - 11:00 AM, Minneapolis Convention Center, Auditorium-Main
* Paul Miller, Colorado Center for Bone Research, USA, Ed McCarthy, John Hopkins Medical School, USA
Purpose: Atypical subtrochanteric femur fractures (ASFF) have been associated with long-term bisphosphonate (BP) administration. The mechanism whereby BP’s may be linked to the greater risk of ASFF is unknown, but may be associated with a reduction in bone remodeling. Recombinant human 1-34 parathyroid hormone (rh-1-34 PTH) increases bone remodeling. It is unknown what effect administration of rh 1-34 PTH may have on remodeling in these patients. We report the results of paired bone biopsies done before and 12 months after treatment with rh 1-34 PTH in 15 patients with bisphosphonate associated ASFF.
Methods: Fifteen post-menopausal women on long-term alendronate who presented with ASFF underwent double tetracycline labeled transiliac bone biopsies between 6 weeks to 7 months following their ASFF. All patients already had intramedullary rods placed. The patients then received teriparatide (rh 1-34 PTH), 20ug/day for 12 months at which time a second biopsy was obtained from the opposite iliac crest. Quantitative histomorphmetric analysis was performed and parameters were compared to published normative reference standards as well as to each patient’s baseline biopsy.
Results: The baseline mineral apposition rate (MAR) in the group averaged 0.278 um/day (normal: 0.66-0.83 um/day) and was zero in 7 patients. After teriparatide administration the average MAR increased to 0.647 um/day. All 7 patients who had immeasurable MAR at baseline increased their MAR following teriparatide (average: 0.673 um/day). Likewise the bone formation rate (BFR) at baseline averaged 1.692 %/yr (normal: 8.6-21.8 %/yr) and was also zero in the same 7 patients that had immeasurable MAR. Following teriparatide the BFR increased in all patients, including the 7 with immeasurable MAR to an average of 4.03 %/yr.
Conclusions: Bone remodeling in patients with bisphosphonate associated ASFF is, on average, lower than published normal reference values but increase after discontinuation of bisphosphonates and 12 months of teriparatide administration. The baseline biopsies were heterogeneous in their quantitative parameters, though 7/15 patients had immeasurable MAR and BFR. The observations in this uncontrolled analysis do not confirm any pathophysiological link between bisphosphonate exposure and the development of ASFF but do suggest that (along with BP discontinuation) teriparatide may increase MAR and BFR in these patients who present with these ASFF. It remains unknown if teriparatide would prevent early fractures from progressing.
* Presenting Authors(s): Paul Miller, Colorado Center for Bone Research, USA