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pharmaceutical agents that cause bone loss

Etiology: 1) anticonvulsants a) phenytoin, phenobarbital, carbamazepine, primidone induce cyt P450 isozyme(s) (cyt P450 3A4?) that enhance metabolism of vitamin D, androgens & estrogens b) valproic acid may increase renal Ca+2 excretion 2) immunosuppressants a) glucocorticoids - reduce Ca+2 absorption & increase Ca+2 excretion - inhibit osteoblasts & activate osteoclasts - suppress androgens & estrogens b) cyclosporine & tacrolimus increase bone resorption c) methotrexate at higher doses reduces osteoblast activity 3) GNRH analogs (leuprolide, nafarelin) antagonize androgen & estrogen 4) thyroxine (excessive) 5) vitamin A (> 10,000 IU/day) 6) vitamin D (> 2000 IU/day) increases bone resorption 7) antidepressants a) SSRI b) lithium carbonate [2] 8) nicotine (smoking) [2] 9) proton pump inhibitor, prolonged use (> 1 year) [2] 10) thiazoladinediones [3] - pioglitazone [4]

General

metabolic agent (metabolic modifier)

References

  1. Prescriber's Letter 11(8): 2004 Drugs and Supplements that Cause Bone Loss Detail-Document#: 200820 (subscription needed) http://www.prescribersletter.com
  2. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  3. NEJM Knowledge+ Endocrinology - Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009 Jan 6;180(1):32-9. Epub 2008 Dec 10. PMID: 19073651 PMCID: PMC2612065 Free PMC article
  4. Viscoli CM et al. Pioglitazone and risk for bone fracture: Safety data from a randomized clinical trial. J Clin Endocrinol Metab 2017 Mar; 102:914 PMID: 27935736 https://academic.oup.com/jcem/article-abstract/102/3/914/3061916/Pioglitazone-and-Risk-for-Bone-Fracture-Safety