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Differential maintenance of cortical and cancellous bone strength following discontinuation of bone-active agents

Journal Article · · Journal of Bone and Mineral Research
DOI:https://doi.org/10.1002/jbmr.249· OSTI ID:1623564
 [1];  [2];  [2];  [3];  [3];  [4];  [2]
  1. University of California Davis Medical Center, Sacramento, CA (United States); DOE/OSTI
  2. University of California Davis Medical Center, Sacramento, CA (United States)
  3. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); University of California, Berkeley, CA (United States)
  4. University of California, Davis, CA (United States)
+ Show Author Affiliations
Osteoporotic patients treated with antiresorptive or anabolic agents experience an increase in bone mass and a reduction in incident fractures. However, the effects of these medications on bone quality and strength after a prolonged discontinuation of treatment are not known. We evaluated these effects in an osteoporotic rat model. Six-month-old ovariectomized (OVX) rats were treated with placebo, alendronate (ALN, 2 mg/kg), parathyroid hormone [PTH(1–34); 20 mg/kg], or raloxifene (RAL, 2 mg/kg) three times a week for 4 months and withdrawn from the treatments for 8 months. Treatment with ALN, PTH, and RAL increased the vertebral trabecular bone volume (BV/TV) by 47%, 53%, and 31%, with corresponding increases in vertebral compression load by 27%, 51%, and 31%, respectively (p < .001). The resulting bone strength was similar to that of the sham-OVX control group with ALN and RAL and higher ( p < .001) with PTH treatment. After 4 months of withdrawal, bone turnover (BFR/BS) remained suppressed in the ALN group versus the OVX controls (p < .001). The vertebral strength was higher than in the OVX group only in ALN-treated group (p < .05), whereas only the PTH-treated animals showed a higher maximum load in tibial bending versus the OVX controls ( p < .05). The vertebral BV/TV returned to the OVX group level in both the PTH and RAL groups 4 months after withdrawal but remained 25% higher than the OVX controls up to 8 months after withdrawal of ALN (p < .05). Interestingly, cortical bone mineral density increased only with PTH treatment (p < .05) but was not different among the experimental groups after withdrawal. At 8 months after treatment withdrawal, none of the treatment groups was different from the OVX control group for cortical or cancellous bone strength. In summary, both ALN and PTH maintained bone strength (maximum load) 4 months after discontinuation of treatment despite changes in bone mass and bone turnover; however, PTH maintained cortical bone strength, whereas ALN maintained cancellous bone strength. Additional studies on the long-term effects on bone strength after discontinuation and with combination of osteoporosis medications are needed to improve our treatment of osteoporosis. 2011 American Society for Bone and Mineral Research.
Research Organization:
None; Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
DOE Contract Number:
AC02-05CH11231
OSTI ID:
1623564
Journal Information:
Journal of Bone and Mineral Research, Journal Name: Journal of Bone and Mineral Research Journal Issue: 3 Vol. 26; ISSN 0884-0431
Publisher:
Wiley
Country of Publication:
United States
Language:
English

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Cited By (1)

Evaluation of bone turnover after bisphosphonate withdrawal and its influence on implant osseointegration: an in vivo study in rats journal August 2018

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59 BASIC BIOLOGICAL SCIENCES
PTH
alendronate
bone strength
endocrinology and metabolism
raloxifene
treatment withdrawal