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Bisphosphonate-associated atypical sub-trochanteric femur fractures: paired bone biopsy quantitative histomorphometry before and after teriparatide administration.
- Source :
-
Seminars in arthritis and rheumatism [Semin Arthritis Rheum] 2015 Apr; Vol. 44 (5), pp. 477-482. Date of Electronic Publication: 2014 Sep 16. - Publication Year :
- 2015
-
Abstract
- Objectives: Bisphosphonate-associated atypical sub-trochanteric femur fractures (ASFF) may be seen with long-term bisphosphonate use, though these fractures are also seen in patients never exposed to bisphosphonates. One theory 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 histomorphometry, has not been observed.<br />Methods: We studied 15 clinic patients referred to The Colorado Center for Bone Research (CCBR) after they had a bisphosphonate-associated ASFF and performed quantitative bone histomorphometry both before and after 12 months of teriparatide (20µg 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 to 7 months after rod placement). Alendronate 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.<br />Results: Three key dynamic histomorphometric features show that 7 of the 15 patients had unmeasurable bone formation, mineralizing surface, and mineral apposition, while the other 8 patients had measurable dynamic parameters; although for all 15 patients, the mean values 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 histomorphometric 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 bisphosphonate and administration of the anabolic agent, teriparatide was associated with improvement in bone turnover.<br />Conclusions: While our study does not establish causality or address the ability of teriparatide to prevent progression of early stress fracture to displaced fractures, it does suggest that teriparatide may improve bone formation in these patients. Our study should stimulate other investigations using larger sample sizes and early stress fractures to see if anabolic agents can reverse these fractures from becoming displaced.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Alendronate administration & dosage
Alendronate therapeutic use
Bone Density Conservation Agents administration & dosage
Bone Density Conservation Agents therapeutic use
Female
Femoral Fractures chemically induced
Humans
Middle Aged
Osteoporosis drug therapy
Osteoporosis pathology
Teriparatide administration & dosage
Teriparatide therapeutic use
Alendronate adverse effects
Bone Density drug effects
Bone Density Conservation Agents adverse effects
Femoral Fractures pathology
Teriparatide adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1532-866X
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Seminars in arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 25312241
- Full Text :
- https://doi.org/10.1016/j.semarthrit.2014.09.005