Abstract
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate – DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).
Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.
This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abrahamsen B, Eiken P, Eastell R (2011) Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med 171:998–1004. https://doi.org/10.1001/archinternmed.2011.20
Ackerman KE, Singhal V, Baskaran C et al (2019) Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial. Br J Sports Med 53:229–236. https://doi.org/10.1136/bjsports-2018-099723
Ahmad AN, Ahmad SN, Ahmad N (2017) HIV infection and bone abnormalities. Open Orthop J 11:777–784. https://doi.org/10.2174/1874325001711010777
Alba M, Xie J, Fung A, Desai M (2016) The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on mineral metabolism and bone in patients with type 2 diabetes mellitus. Curr Med Res Opin 32:1375–1385. https://doi.org/10.1080/03007995.2016.1174841
Altayar O, Al Nofal A, Carranza Leon BG et al (2017) Treatments to prevent bone loss in functional hypothalamic amenorrhea: a systematic review and meta-analysis. J Endocr Soc 1:500–511. https://doi.org/10.1210/js.2017-00102
Avila ML, Pullenayegum E, Williams S et al (2016) Timing of low bone mineral density and predictors of bone mineral density trajectory in children on long-term warfarin: a longitudinal study. Osteoporos Int 27:1547–1557. https://doi.org/10.1007/s00198-015-3411-8
Baker JF, Long J, Mostoufi-Moab S et al (2017) Muscle deficits in rheumatoid arthritis contribute to inferior cortical bone structure and trabecular bone mineral density. J Rheumatol 44:1777–1785. https://doi.org/10.3899/jrheum.170513
Barnes C, Newall F, Ignjatovic V et al (2005) Reduced bone density in children on long-term warfarin. Pediatr Res 57:578–581. https://doi.org/10.1203/01.PDR.0000155943.07244.04
Bazelier MT, Gallagher AM, van Staa T-P et al (2012a) Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Pharmacoepidemiol Drug Saf 21:507–514. https://doi.org/10.1002/pds.3234
Bazelier MT, Vestergaard P, Gallagher AM et al (2012b) Risk of fracture with thiazolidinediones: disease or drugs? Calcif Tissue Int 90:450–457. https://doi.org/10.1007/s00223-012-9591-8
Beck GR, Khazai NB, Bouloux GF et al (2013) The effects of thiazolidinediones on human bone marrow stromal cell differentiation in vitro and in thiazolidinedione-treated patients with type 2 diabetes. Transl Res 161:145–155. https://doi.org/10.1016/j.trsl.2012.08.006
Beksinska ME, Kleinschmidt I, Smit JA (2018) Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status. Womens Midlife Health 4:6. https://doi.org/10.1186/s40695-018-0035-0
Beljan JR, Hellewell AB (1977) The effect of chronic heparin administration on the mineralization of an experimental osseous defect. Clin Orthop Relat Res:205–207
Beniczky SA, Viken J, Jensen LT, Andersen NB (2012) Bone mineral density in adult patients treated with various antiepileptic drugs. Seizure 21:471–472. https://doi.org/10.1016/j.seizure.2012.04.002
Billington EO, Grey A, Bolland MJ (2015) The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis. Diabetologia 58:2238–2246. https://doi.org/10.1007/s00125-015-3660-2
Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P (2008) Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol 47:747–754. https://doi.org/10.1080/02841860802001467
Bleicher K, Cumming RG, Naganathan V et al (2013) Predictors of the rate of BMD loss in older men: findings from the CHAMP study. Osteoporos Int 24:1951–1963. https://doi.org/10.1007/s00198-012-2226-0
Bozkurt N, Erdem M, Yilmaz E et al (2009) The relationship of homocyteine, B12 and folic acid with the bone mineral density of the femur and lumbar spine in Turkish postmenopausal women. Arch Gynecol Obstet 280:381–387. https://doi.org/10.1007/s00404-009-0936-0
Buckley LM, Leib ES, Cartularo KS et al (1997) Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 24:1489–1494
Bulut SD, Bulut S, Atalan DG et al (2016) The effect of antipsychotics on bone mineral density and sex hormones in male patients with schizophrenia. Psychiatr Danub 28:255–262
Cansu A, Yesilkaya E, Serdaroğlu A et al (2008) Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol 39:266–271. https://doi.org/10.1016/j.pediatrneurol.2008.07.001
Carbone LD, Kaeley G, McKown KM et al (1999) Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis. Calcif Tissue Int 64:100–101
Carbone LD, Tylavsky FA, Cauley JA et al (2003) Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res 18:1795–1802. https://doi.org/10.1359/jbmr.2003.18.10.1795
Cetinkaya Y, Kurtulmuş YS, Tutkavul K, Tireli H (2009) The effect of oxcarbazepine on bone metabolism. Acta Neurol Scand 120:170–175. https://doi.org/10.1111/j.1600-0404.2008.01148.x
Cezarino PYA, Simões RDS, Baracat EC, Soares JM Jr (2018) Are women living with HIV prone to osteoporosis in postmenopause? A systematic review. Rev Assoc Med Bras 64:469–473. https://doi.org/10.1590/1806-9282.64.05.469
Chen Y-M, Chen H-H, Huang W-N et al (2017) Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis. PLoS One 12:e0188454. https://doi.org/10.1371/journal.pone.0188454
Chen W, Johnson KM, FitzGerald JM et al (2018) Long-term effects of inhaled corticosteroids on bone mineral density in older women with asthma or COPD: a registry-based cohort study. Arch Osteoporos 13:116. https://doi.org/10.1007/s11657-018-0537-2
Cheng L, Zhang K, Zhang Z (2018) Effectiveness of thiazides on serum and urinary calcium levels and bone mineral density in patients with osteoporosis: a systematic review and meta-analysis. Drug Des Devel Ther 12:3929–3935. https://doi.org/10.2147/DDDT.S179568
Cho YH, Um MJ, Kim SJ et al (2016) Raloxifene administration in women treated with long term gonadotropin-releasing hormone agonist for severe endometriosis: effects on bone mineral density. J Menopausal Med 22:174–179. https://doi.org/10.6118/jmm.2016.22.3.174
Chou I-J, Lin K-L, Wang H-S, Wang C-J (2007) Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy. Acta Paediatr Taiwan 48:317–322
Ciccullo A, D’Avino A, Lassandro AP et al (2018) Changes in bone mineral density in HIV-positive, virologically suppressed patients switching to lamivudine/dolutegravir dual therapy: preliminary results from clinical practice. Infez Med 26:336–340
Coluzzi F, Pergolizzi J, Raffa RB, Mattia C (2015) The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism. Ther Clin Risk Manag 11:515–523. https://doi.org/10.2147/TCRM.S79409
Coluzzi F, Billeci D, Maggi M, Corona G (2018) Testosterone deficiency in non-cancer opioid-treated patients. J Endocrinol Investig 41:1377–1388. https://doi.org/10.1007/s40618-018-0964-3
Conesa-Buendía FM, Llamas-Granda P, Larrañaga-Vera A et al (2019) Tenofovir causes bone loss via decreased bone formation and increased bone resorption, which can be counteracted by dipyridamole in mice. J Bone Miner Res 34:923–938. https://doi.org/10.1002/jbmr.3665
Coppola G, Fortunato D, Auricchio G et al (2009) Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia 50:2140–2146. https://doi.org/10.1111/j.1528-1167.2009.02082.x
Costagliola D, Potard V, Lang S et al (2019) Impact of antiretroviral drugs on fracture risk in HIV-infected individuals: a case-control study nested within the French hospital database on HIV (FHDH-ANRS CO4). J Acquir Immune Defic Syndr 80:214–223. https://doi.org/10.1097/QAI.0000000000001903
Crandall C (2004) Vitamin A intake and osteoporosis: a clinical review. J Women’s Health 13:939–953. https://doi.org/10.1089/jwh.2004.13.939
da Rizzo CB, Goldberg TBL, Biason TP et al (2018) One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives. J Pediatr 95:567–574. https://doi.org/10.1016/j.jped.2018.05.011
Dahlman TC, Sjöberg HE, Ringertz H (1994) Bone mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol 170:1315–1320
de Laet C, Kanis JA, Odén A et al (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338. https://doi.org/10.1007/s00198-005-1863-y
di Mase R, Cerbone M, Improda N et al (2012) Bone health in children with long-term idiopathic subclinical hypothyroidism. Ital J Pediatr 38:56. https://doi.org/10.1186/1824-7288-38-56
Diem SJ, Blackwell TL, Stone KL et al (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167:1240–1245. https://doi.org/10.1001/archinte.167.12.1240
Diem SJ, Ruppert K, Cauley JA et al (2013) Rates of bone loss among women initiating antidepressant medication use in midlife. J Clin Endocrinol Metab 98:4355–4363. https://doi.org/10.1210/jc.2013-1971
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2015) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 386:1341–1352. https://doi.org/10.1016/S0140-6736(15)61074-1
Eastell R, Adams JE, Coleman RE et al (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26:1051–1057. https://doi.org/10.1200/JCO.2007.11.0726
Eastell R, Adams J, Clack G et al (2011) Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol 22:857–862. https://doi.org/10.1093/annonc/mdq541
El-Haggar SM, Mostafa TM, Allah HMS, Akef GH (2018) Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients. Arq Neuropsiquiatr 76:452–458. https://doi.org/10.1590/0004-282X20180068
Ensrud KE, Walczak TS, Blackwell T et al (2004) Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology 62:2051–2057
Farhat G, Yamout B, Mikati MA et al (2002) Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 58:1348–1353
Feldkamp J, Becker A, Witte OW et al (2000) Long-term anticonvulsant therapy leads to low bone mineral density--evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Exp Clin Endocrinol Diabetes 108:37–43
Francis PA, Pagani O, Fleming GF et al (2018) Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med 379:122–137. https://doi.org/10.1056/NEJMoa1803164
Freundlich M (2006) Bone mineral content and mineral metabolism during cyclosporine treatment of nephrotic syndrome. J Pediatr 149:383–389. https://doi.org/10.1016/j.jpeds.2006.04.060
Fuglsang-Nielsen R, Starup-Linde J, Gregersen S, Vestergaard P (2018) The effect of meals on bone turnover – a systematic review with focus on diabetic bone disease. Expert Rev Endocrinol Metab 13:233–249. https://doi.org/10.1080/17446651.2018.1518131
Gajic-Veljanoski O, Phua CW, Shah PS, Cheung AM (2016) Effects of long-term low-molecular-weight heparin on fractures and bone density in non-pregnant adults: a systematic review with meta-analysis. J Gen Intern Med 31:947–957. https://doi.org/10.1007/s11606-016-3603-8
Galambosi P, Hiilesmaa V, Ulander V-M et al (2016) Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density. Thromb Res 143:122–126. https://doi.org/10.1016/j.thromres.2016.05.016
Gersten J, Hsieh J, Weiss H, Ricciotti NA (2016) Effect of extended 30 μg ethinyl estradiol with continuous low-dose ethinyl estradiol and cyclic 20 μg ethinyl estradiol oral contraception on adolescent bone density: a randomized trial. J Pediatr Adolesc Gynecol 29:635–642. https://doi.org/10.1016/j.jpag.2016.05.012
Giangregorio LM, Leslie WD, Lix LM et al (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308. https://doi.org/10.1002/jbmr.556
Gissel T, Poulsen CS, Vestergaard P (2007) Adverse effects of antiepileptic drugs on bone mineral density in children. Expert Opin Drug Saf 6:267–278. https://doi.org/10.1517/14740338.6.3.267
Goerss JB, Kim CH, Atkinson EJ et al (1992) Risk of fractures in patients with pernicious anemia. J Bone Miner Res 7:573–579. https://doi.org/10.1002/jbmr.5650070514
Goldvaser H, Barnes TA, Šeruga B et al (2018) Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst 110:31–39. https://doi.org/10.1093/jnci/djx141
Gomez L, Stubbs B, Shirazi A et al (2016) Lower bone mineral density at the hip and lumbar spine in people with psychosis versus controls: a comprehensive review and skeletal site-specific meta-analysis. Curr Osteoporos Rep 14:249–259. https://doi.org/10.1007/s11914-016-0325-0
Gotthardt F, Huber C, Thierfelder C et al (2017) Bone mineral density and its determinants in men with opioid dependence. J Bone Miner Metab 35:99–107. https://doi.org/10.1007/s00774-015-0732-9
Güerri-Fernandez R, Vestergaard P, Carbonell C et al (2013) HIV infection is strongly associated with hip fracture risk, independently of age, gender, and comorbidities: a population-based cohort study. J Bone Miner Res 28:1259–1263. https://doi.org/10.1002/jbmr.1874
Hakami T, O’Brien TJ, Petty SJ et al (2016) Monotherapy with levetiracetam versus older AEDs: a randomized comparative trial of effects on bone health. Calcif Tissue Int 98:556–565. https://doi.org/10.1007/s00223-016-0109-7
Heemstra KA, Hamdy NAT, Romijn JA, Smit JWA (2006) The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Thyroid 16:583–591. https://doi.org/10.1089/thy.2006.16.583
Heo K, Rhee Y, Lee HW et al (2011) The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy. Epilepsia 52:1884–1889. https://doi.org/10.1111/j.1528-1167.2011.03131.x
Heo JH, Rascati KL, Lopez KN, Moffett BS (2018) Increased fracture risk with furosemide use in children with congenital heart disease. J Pediatr 199:92–98.e10. https://doi.org/10.1016/j.jpeds.2018.03.077
Hong AR, Kim JH, Lee KH et al (2017) Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer. Osteoporos Int 28:1413–1422. https://doi.org/10.1007/s00198-016-3899-6
Hung S-C, Lin C-H, Hung H-C et al (2017) Use of selective serotonin reuptake inhibitors and risk of hip fracture in the elderly: a case-control study in Taiwan. J Am Med Dir Assoc 18:350–354. https://doi.org/10.1016/j.jamda.2016.12.003
Ito T, Jensen RT (2010) Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr Gastroenterol Rep 12:448–457. https://doi.org/10.1007/s11894-010-0141-0
Kakehasi AM, Carvalho AV, Maksud FAN, Barbosa AJA (2012) Serum levels of vitamin B12 are not related to low bone mineral density in postmenopausal Brazilian women. Rev Bras Reumatol 52:863–869
Killinger Z, Gajdarova L, Kuzma M et al (2018) Biologic treatment in comparison to methotrexate has positive effect on trabecular bone score in rheumatoid arthritis patients: 1-year follow-up. Acta Clin Belg 74:121–125. https://doi.org/10.1080/17843286.2018.1512189
Kim SH, Joung JY, Kim S et al (2017) Comparison of bone mineral loss by combined androgen block agonist versus GnRH in patients with prostate cancer: a 12 month-prospective observational study. Sci Rep 7:39562. https://doi.org/10.1038/srep39562
Kinjo M, Setoguchi S, Schneeweiss S, Solomon DH (2005) Bone mineral density in subjects using central nervous system-active medications. Am J Med 118:1414. https://doi.org/10.1016/j.amjmed.2005.07.033
Koo DL, Hwang KJ, Han SW et al (2014) Effect of oxcarbazepine on bone mineral density and biochemical markers of bone metabolism in patients with epilepsy. Epilepsy Res 108:442–447. https://doi.org/10.1016/j.eplepsyres.2013.09.009
Kristensen B, Ejlertsen B, Mouridsen HT et al (1996) Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen. Breast Cancer Res Treat 39:321–326
Kristensen B, Ejlertsen B, Jensen M-B et al (2018) The occurrence of fractures after adjuvant treatment of breast cancer: a DBCG register study. Acta Oncol 57:141–145. https://doi.org/10.1080/0284186X.2017.1403043
Kulak CAM, Borba VZC, Silvado CE et al (2007) Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy. Arq Bras Endocrinol Metabol 51:466–471
Kwan ML, Yao S, Laurent CA et al (2018) Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy. Breast Cancer Res Treat 168:523–530. https://doi.org/10.1007/s10549-017-4626-5
Kwon OC, Oh JS, Hong S et al (2019) Conventional synthetic disease-modifying antirheumatic drugs and bone mineral density in rheumatoid arthritis patients with osteoporosis: possible beneficial effect of leflunomide. Clin Exp Rheumatol 37:813–819
Kyvernitakis I, Kostev K, Nassour T et al (2017) The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK. Osteoporos Int 28:291–297. https://doi.org/10.1007/s00198-016-3714-4
Kyvernitakis I, Kostev K, Hadji P (2018) The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer. Osteoporos Int 29:2557–2564. https://doi.org/10.1007/s00198-018-4642-2
Laan RF, van Riel PL, van de Putte LB et al (1993) Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 15:963–968
Lai S-W, Cheng K-C, Lin C-L, Liao K-F (2017) Furosemide use and acute risk of hip fracture in older people: a nationwide case-control study in Taiwan. Geriatr Gerontol Int 17:2552–2558. https://doi.org/10.1111/ggi.13087
Lange HLH, Manos BE, Gothard MD et al (2017) Bone mineral density and weight changes in adolescents randomized to 3 doses of depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 30:169–175. https://doi.org/10.1016/j.jpag.2016.10.011
Leach MJ, Pratt NL, Roughead EE (2017) The risk of hip fracture due to mirtazapine exposure when switching antidepressants or using other antidepressants as add-on therapy. Drugs Real World Outcomes 4:247–255. https://doi.org/10.1007/s40801-017-0120-y
Lee RH, Lyles KW, Colón-Emeric C (2010) A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatr Pharmacother 8:34–46. https://doi.org/10.1016/j.amjopharm.2010.02.003
Lee D-Y, Lee J-Y, Seo J-W et al (2016) Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis. Arch Gynecol Obstet 294:1257–1263. https://doi.org/10.1007/s00404-016-4184-9
Lee S-H, Hsu W-T, Lai C-C et al (2017) Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis. Osteoporos Int 28:1167–1178. https://doi.org/10.1007/s00198-016-3881-3
Lenaers-Claeys G, Vaes G (1979) Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin. Biochim Biophys Acta 584:375–388
Leuschner M, Maier KP, Schlichting J et al (1999) Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 117:918–925
Lim LS, Fink HA, Kuskowski MA et al (2005) Diuretic use and bone mineral density in older USA men: the osteoporotic fractures in men (MrOS) study. Age Ageing 34:504–507. https://doi.org/10.1093/ageing/afi133
Lim LS, Fink HA, Kuskowski MA et al (2008) Loop diuretic use and increased rates of hip bone loss in older men: the Osteoporotic Fractures in Men Study. Arch Intern Med 168:735–740. https://doi.org/10.1001/archinte.168.7.735
Lima CA, Lyra AC, Mendes CMC et al (2017) Bone mineral density and inflammatory bowel disease severity. Braz J Med Biol Res 50:e6374. https://doi.org/10.1590/1414-431X20176374
Lionikaite V, Gustafsson KL, Westerlund A et al (2018) Clinically relevant doses of vitamin A decrease cortical bone mass in mice. J Endocrinol 239:389–402. https://doi.org/10.1530/JOE-18-0316
Liu J, Li X, Fan L et al (2019) Proton pump inhibitors therapy and risk of bone diseases: an update meta-analysis. Life Sci 218:213–223. https://doi.org/10.1016/j.lfs.2018.12.058
Lopez LM, Chen M, Mullins Long S et al (2015) Steroidal contraceptives and bone fractures in women: evidence from observational studies. Cochrane Database Syst Rev 7:CD009849. https://doi.org/10.1002/14651858.CD009849.pub3
Markopoulos C, Koukouras D, Venizelos V et al (2016) Impact of chemotherapy followed by aromatase inhibitors on bone health of women with ER-positive early breast cancer in real world clinical settings in Greece: results of the POCHARBI trial conducted by the Hellenic Society of Breast Surgeons. Breast 27:27–34. https://doi.org/10.1016/j.breast.2016.02.007
Masamoto K, Otsuki B, Fujibayashi S et al (2018) Factors influencing spinal sagittal balance, bone mineral density, and Oswestry Disability Index outcome measures in patients with rheumatoid arthritis. Eur Spine J 27:406–415. https://doi.org/10.1007/s00586-017-5401-3
Masunari N, Fujiwara S, Nakata Y et al (2008) Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese. Hiroshima J Med Sci 57:17–25
Miyaji Y, Saika T, Yamamoto Y et al (2004) Effects of gonadotropin-releasing hormone agonists on bone metabolism markers and bone mineral density in patients with prostate cancer. Urology 64:128–131. https://doi.org/10.1016/j.urology.2004.03.012
Modesto W, Bahamondes MV, Silva dos Santos P et al (2014) Exploratory study of the effect of lifestyle counselling on bone mineral density and body composition in users of the contraceptive depot-medroxyprogesterone acetate. Eur J Contracept Reprod Health Care 19:244–249. https://doi.org/10.3109/13625187.2014.924098
Moon J-Y, Sin DD (2019) Inhaled corticosteroids and fractures in chronic obstructive pulmonary disease: current understanding and recommendations. Curr Opin Pulm Med 25:165–172. https://doi.org/10.1097/MCP.0000000000000554
Moro-Alvarez MJ, Díaz Curiel M, de la Piedra C et al (2009) Bone disease induced by phenytoin therapy: clinical and experimental study. Eur Neurol 62:219–230. https://doi.org/10.1159/000229309
Namba S, Yamaoka-Tojo M, Kakizaki R et al (2017) Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation. Heart Vessel 32:977–982. https://doi.org/10.1007/s00380-017-0950-2
Nassar Y, Richter S (2018) Proton-pump inhibitor use and fracture risk: an updated systematic review and meta-analysis. J Bone Metab 25:141–151. https://doi.org/10.11005/jbm.2018.25.3.141
Nishiyama M, Itoh F, Ujiie A (1997) Low-molecular-weight heparin (dalteparin) demonstrated a weaker effect on rat bone metabolism compared with heparin. Jpn J Pharmacol 74:59–68
O’Rourke TK, Wosnitzer MS (2016) Opioid-induced androgen deficiency (OPIAD): diagnosis, management, and literature review. Curr Urol Rep 17:76. https://doi.org/10.1007/s11934-016-0634-y
Oshagbemi OA, Burden AM, Shudofsky KN et al (2018) Use of high-dose intermittent systemic glucocorticoids and the risk of fracture in patients with chronic obstructive pulmonary disease. Bone 110:238–243. https://doi.org/10.1016/j.bone.2018.02.007
Pack AM, Morrell MJ, Randall A et al (2008) Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology 70:1586–1593. https://doi.org/10.1212/01.wnl.0000310981.44676.de
Palermo A, D’Onofrio L, Eastell R et al (2015) Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review. Osteoporos Int 26:2073–2089. https://doi.org/10.1007/s00198-015-3123-0
Patschan D, Loddenkemper K, Buttgereit F (2001) Molecular mechanisms of glucocorticoid-induced osteoporosis. Bone 29:498–505
Pavlova V, Filipova E, Uzunova K et al (2018) Pioglitazone therapy and fractures: systematic review and meta-analysis. Endocr Metab Immune Disord Drug Targets 18:502–507. https://doi.org/10.2174/1871530318666180423121833
Pérez-Sáez MJ, Herrera S, Prieto-Alhambra D et al (2018) Maintenance low dose systemic glucocorticoids have limited impact on bone strength and mineral density among incident renal allograft recipients: a pilot prospective cohort study. Bone 116:290–294. https://doi.org/10.1016/j.bone.2018.08.013
Pettilä V, Leinonen P, Markkola A et al (2002) Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 87:182–186
Phabphal K, Geater A, Limapichart K et al (2013) The association between BsmI polymorphism and bone mineral density in young patients with epilepsy who are taking phenytoin. Epilepsia 54:249–255. https://doi.org/10.1111/epi.12049
Prieto-Alhambra D, Güerri-Fernández R, de Vries F et al (2014) HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study. J Acquir Immune Defic Syndr 66:90–95. https://doi.org/10.1097/QAI.0000000000000112
Rahimdel A, Dehghan A, Moghadam MA, Ardekani AM (2016) Relationship between bone density and biochemical markers of bone among two groups taking carbamazepine and sodium valproate for epilepsy in comparison with healthy individuals in Yazd. Electron Physician 8:3257–3265. https://doi.org/10.19082/3257
Rauma PH, Honkanen RJ, Williams LJ et al (2016) Effects of antidepressants on postmenopausal bone loss – a 5-year longitudinal study from the OSTPRE cohort. Bone 89:25–31. https://doi.org/10.1016/j.bone.2016.05.003
Rejnmark L, Vestergaard P, Heickendorff L et al (2001) Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women. Eur J Clin Investig 31:764–772
Rejnmark L, Buus NH, Vestergaard P et al (2004a) Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res 19:737–744. https://doi.org/10.1359/JBMR.040209
Rejnmark L, Vestergaard P, Charles P et al (2004b) No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women. Osteoporos Int 15:872–880. https://doi.org/10.1007/s00198-004-1618-1
Rejnmark L, Vestergaard P, Mosekilde L (2005) Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int 76:167–175. https://doi.org/10.1007/s00223-004-0084-2
Rejnmark L, Vestergaard P, Mosekilde L (2006a) Fracture risk in patients treated with loop diuretics. J Intern Med 259:117–124. https://doi.org/10.1111/j.1365-2796.2005.01585.x
Rejnmark L, Vestergaard P, Mosekilde L (2006b) Statin but not non-statin lipid-lowering drugs decrease fracture risk: a nation-wide case-control study. Calcif Tissue Int 79:27–36. https://doi.org/10.1007/s00223-006-0024-4
Rejnmark L, Vestergaard P, Mosekilde L (2007) Fracture risk in users of oral anticoagulants: a nationwide case-control study. Int J Cardiol 118:338–344. https://doi.org/10.1016/j.ijcard.2006.07.022
Saggese G, Bertelloni S, Baroncelli GI et al (1996) Bone mineral density in adolescent females treated with L-thyroxine: a longitudinal study. Eur J Pediatr 155:452–457
Schoon EJ, Bollani S, Mills PR et al (2005) Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease. Clin Gastroenterol Hepatol 3:113–121
Schweiger JU, Schweiger U, Hüppe M et al (2018) The use of antidepressive agents and bone mineral density in women: a meta-analysis. Int J Environ Res Public Health 15:E1373. https://doi.org/10.3390/ijerph15071373
Segna D, Bauer DC, Feller M et al (2018) Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med 283:56–72. https://doi.org/10.1111/joim.12688
Sheth RD, Hermann BP (2007) Bone mineral density with lamotrigine monotherapy for epilepsy. Pediatr Neurol 37:250–254. https://doi.org/10.1016/j.pediatrneurol.2007.05.018
Shiek Ahmad B, O’Brien TJ, Gorelik A et al (2016) Bone mineral changes in epilepsy patients during initial years of antiepileptic drug therapy. J Clin Densitom 19:450–456. https://doi.org/10.1016/j.jocd.2016.07.008
Shimizu C, Fujita T, Fuke Y et al (2013) Effects of cyclosporine on bone mineral density in patients with glucocorticoid-dependent nephrotic syndrome in remission. Int Urol Nephrol 45:803–808. https://doi.org/10.1007/s11255-012-0264-3
Sieber PR, Keiller DL, Kahnoski RJ et al (2004) Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol 171:2272–2276, quiz 2435
Smith MR, Goode M, Zietman AL et al (2004) Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 22:2546–2553. https://doi.org/10.1200/JCO.2004.01.174
Smith MR, Lee WC, Brandman J et al (2005) Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 23:7897–7903. https://doi.org/10.1200/JCO.2004.00.6908
Stenova E, Steno B, Killinger Z et al (2011) Effect of long-term oral anticoagulant therapy on bone mineral density and bone turnover markers: a prospective 12 month study. Bratisl Lek Listy 112:71–76
Sugiyama T, Takaki T, Sakanaka K et al (2007) Warfarin-induced impairment of cortical bone material quality and compensatory adaptation of cortical bone structure to mechanical stimuli. J Endocrinol 194:213–222. https://doi.org/10.1677/JOE-07-0119
Suljic EM, Mehicevic A, Mahmutbegovic N (2018) Effect of long-term carbamazepine therapy on bone health. Med Arch 72:262–266. https://doi.org/10.5455/medarh.2018.72.262-266
Svendsen P, Shekhrajka N, Nielsen KL et al (2017) R-CHOP(-like) treatment of diffuse large B-cell lymphoma significantly reduces CT-assessed vertebral bone density: a single center study of 111 patients. Leuk Lymphoma 58:1105–1113. https://doi.org/10.1080/10428194.2016.1233543
Tattersfield AE, Town GI, Johnell O et al (2001) Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax 56:272–278
Trémollières F, Pouillès JM, Louvet JP, Ribot C (1991) Transitory bone loss during substitution treatment for hypothyroidism. Results of a two year prospective study. Rev Rhum Mal Osteoartic 58:869–875
Tseng P-T, Chen Y-W, Yeh P-Y et al (2015) Bone mineral density in schizophrenia: an update of current meta-analysis and literature review under guideline of PRISMA. Medicine (Baltimore) 94:e1967. https://doi.org/10.1097/MD.0000000000001967
Tseng OL, Spinelli JJ, Gotay CC et al (2018) Aromatase inhibitors are associated with a higher fracture risk than tamoxifen: a systematic review and meta-analysis. Ther Adv Musculoskelet Dis 10:71–90. https://doi.org/10.1177/1759720X18759291
van der Wiel HE, Lips P, Huijgens PC, Netelenbos JC (1993) Effects of short-term low-dose heparin administration on biochemical parameters of bone turnover. Bone Miner 22:27–32
van Staa TP, Laan RF, Barton IP et al (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229. https://doi.org/10.1002/art.11283
Vestergaard P (2005) Epilepsy, osteoporosis and fracture risk – a meta-analysis. Acta Neurol Scand 112:277–286. https://doi.org/10.1111/j.1600-0404.2005.00474.x
Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int 18:427–444. https://doi.org/10.1007/s00198-006-0253-4
Vestergaard P (2008a) Skeletal effects of drugs to treat cancer. Curr Drug Saf 3:173–177
Vestergaard P (2008b) Pain-relief medication and risk of fractures. Curr Drug Saf 3:199–203
Vestergaard P (2015a) Bone: fracture risk in the JUPITER trial--statin treatment or not? Nat Rev Endocrinol 11:135–136. https://doi.org/10.1038/nrendo.2014.232
Vestergaard P (2015b) Effects of antiepileptic drugs on bone health and growth potential in children with epilepsy. Paediatr Drugs 17:141–150. https://doi.org/10.1007/s40272-014-0115-z
Vestergaard P, Mosekilde L (2003) Hyperthyroidism, bone mineral, and fracture risk--a meta-analysis. Thyroid 13:585–593. https://doi.org/10.1089/105072503322238854
Vestergaard P, Weeke J, Hoeck HC et al (2000) Fractures in patients with primary idiopathic hypothyroidism. Thyroid 10:335–340. https://doi.org/10.1089/thy.2000.10.335
Vestergaard P, Jørgensen JOL, Hagen C et al (2002) Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study. Clin Endocrinol 56:159–167
Vestergaard P, Rejnmark L, Mosekilde L (2004) Fracture risk associated with use of antiepileptic drugs. Epilepsia 45:1330–1337. https://doi.org/10.1111/j.0013-9580.2004.18804.x
Vestergaard P, Rejnmark L, Mosekilde L (2005) Fracture risk associated with systemic and topical corticosteroids. J Intern Med 257:374–384. https://doi.org/10.1111/j.1365-2796.2005.01467.x
Vestergaard P, Rejnmark L, Mosekilde L (2006a) Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 79:76–83. https://doi.org/10.1007/s00223-006-0021-7
Vestergaard P, Rejnmark L, Mosekilde L (2006b) Methotrexate, azathioprine, cyclosporine, and risk of fracture. Calcif Tissue Int 79:69–75. https://doi.org/10.1007/s00223-006-0060-0
Vestergaard P, Rejnmark L, Mosekilde L (2006c) Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis. Calcif Tissue Int 79:84–94. https://doi.org/10.1007/s00223-006-0020-8
Vestergaard P, Rejnmark L, Mosekilde L (2006d) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17:807–816. https://doi.org/10.1007/s00198-005-0065-y
Vestergaard P, Rejnmark L, Mosekilde L (2007) Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids. Chest 132:1599–1607. https://doi.org/10.1378/chest.07-1092
Vestergaard P, Rejnmark L, Mosekilde L (2008a) The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women. Contraception 78:459–464. https://doi.org/10.1016/j.contraception.2008.07.014
Vestergaard P, Rejnmark L, Mosekilde L (2008b) Fracture risk in very young women using combined oral contraceptives. Contraception 78:358–364. https://doi.org/10.1016/j.contraception.2008.06.010
Vestergaard P, Rejnmark L, Mosekilde L (2008c) Fracture risk associated with different types of oral corticosteroids and effect of termination of corticosteroids on the risk of fractures. Calcif Tissue Int 82:249–257. https://doi.org/10.1007/s00223-008-9124-7
Vestergaard P, Rejnmark L, Mosekilde L (2008d) Effect of tamoxifen and aromatase inhibitors on the risk of fractures in women with breast cancer. Calcif Tissue Int 82:334–340. https://doi.org/10.1007/s00223-008-9132-7
Vestergaard P, Rejnmark L, Mosekilde L (2008e) Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int 82:92–101. https://doi.org/10.1007/s00223-007-9099-9
Vestergaard P, Rejnmark L, Mosekilde L (2008f) Anxiolytics and sedatives and risk of fractures: effects of half-life. Calcif Tissue Int 82:34–43. https://doi.org/10.1007/s00223-007-9095-0
Vestergaard P, Rejnmark L, Mosekilde L (2010) High-dose treatment with vitamin A analogues and risk of fractures. Arch Dermatol 146:478–482. https://doi.org/10.1001/archdermatol.2010.59
Vestergaard P, Hermann P, Jensen J-EB et al (2012) Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS). Osteoporos Int 23:1255–1265. https://doi.org/10.1007/s00198-011-1692-0
Vestergaard P, Prieto-Alhambra D, Javaid MK, Cooper C (2013) Fractures in users of antidepressants and anxiolytics and sedatives: effects of age and dose. Osteoporos Int 24:671–680. https://doi.org/10.1007/s00198-012-2043-5
Wadhwa VK, Weston R, Mistry R, Parr NJ (2009) Long-term changes in bone mineral density and predicted fracture risk in patients receiving androgen-deprivation therapy for prostate cancer, with stratification of treatment based on presenting values. BJU Int 104:800–805. https://doi.org/10.1111/j.1464-410X.2009.08483.x
Wadhwa VK, Weston R, Parr NJ (2011) Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer. BJU Int 107:1923–1929. https://doi.org/10.1111/j.1464-410X.2010.09726.x
WHOCC (n.d.) ATC/DDD Index. https://www.whocc.no/atc_ddd_index/. Accessed 25 Feb 2019
Williams LJ, Pasco JA, Henry MJ et al (2011) Paracetamol (acetaminophen) use, fracture and bone mineral density. Bone 48:1277–1281. https://doi.org/10.1016/j.bone.2011.03.435
Wong CA, Walsh LJ, Smith CJ et al (2000) Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 355:1399–1403. https://doi.org/10.1016/S0140-6736(00)02138-3
Wu Q, Qu W, Crowell MD et al (2013) Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies. J Bone Miner Res 28:753–763. https://doi.org/10.1002/jbmr.1813
Ye Y, Zhao C, Liang J et al (2018) Effect of sodium-glucose co-transporter 2 inhibitors on bone metabolism and fracture risk. Front Pharmacol 9:1517. https://doi.org/10.3389/fphar.2018.01517
Zhang J, Wang K-X, Wei Y et al (2010) Effect of topiramate and carbamazepine on bone metabolism in children with epilepsy. Zhongguo Dang Dai Er Ke Za Zhi 12:96–98
Zhang M-H, Zhang W, Zhang A-D et al (2013) Effect of depot medroxyprogesterone acetate on bone mineral density in adolescent women. Chin Med J 126:4043–4047
Zhang X, Zhang R, Moore JB et al (2017) The effect of vitamin A on fracture risk: a meta-analysis of cohort studies. Int J Environ Res Public Health 14:1043. https://doi.org/10.3390/ijerph14091043
Zhu Z-N, Jiang Y-F, Ding T (2014) Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone 68:115–123. https://doi.org/10.1016/j.bone.2014.08.010
Zidan J, Keidar Z, Basher W, Israel O (2004) Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer. Med Oncol 21:117–121. https://doi.org/10.1385/MO:21:2:117
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Vestergaard, P. (2019). Drugs Causing Bone Loss. In: Stern, P.H. (eds) Bone Regulators and Osteoporosis Therapy. Handbook of Experimental Pharmacology, vol 262. Springer, Cham. https://doi.org/10.1007/164_2019_340
Download citation
DOI: https://doi.org/10.1007/164_2019_340
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-57377-5
Online ISBN: 978-3-030-57378-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)