Drug-induced bone loss: a major safety concern in Europe

ABSTRACT Introduction: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries. Areas covered: Beyond glucorticoid – the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors. Expert opinion: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.

[1]  S. Kerr,et al.  Zoledronic acid is superior to tenofovir disoproxil fumarate-switching for low bone mineral density in adults with HIV , 2018, AIDS.

[2]  S. Matsushita,et al.  Osteoporosis-Related Fractures in HIV-Infected Patients Receiving Long-Term Tenofovir Disoproxil Fumarate: An Observational Cohort Study , 2018, Drug Safety.

[3]  S. Haneuse,et al.  Effects of analgesics on bone mineral density: A longitudinal analysis of the prospective SWAN cohort with three‐group matching weights , 2018, Pharmacoepidemiology and drug safety.

[4]  M. Bolster,et al.  Drugs that may harm bone: Mitigating the risk , 2016, Cleveland Clinic Journal of Medicine.

[5]  A. Cheung,et al.  Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis , 2016, Journal of General Internal Medicine.

[6]  E. Lewiecki,et al.  Drug-induced osteoporosis: from Fuller Albright to aromatase inhibitors , 2015, Climacteric : the journal of the International Menopause Society.

[7]  G. Sergi,et al.  Vitamin K antagonists' use and fracture risk: results from a systematic review and meta‐analysis , 2015, Journal of thrombosis and haemostasis : JTH.

[8]  K. Curtis,et al.  Steroidal contraceptives and bone fractures in women: evidence from observational studies. , 2015, The Cochrane database of systematic reviews.

[9]  C. Roux,et al.  Glucocorticoid-induced osteoporosis , 2015, RMD Open.

[10]  M. Wissing Chemotherapy- and Irradiation-Induced Bone Loss in Adults with Solid Tumors , 2015, Current Osteoporosis Reports.

[11]  T. Stürmer,et al.  Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older , 2015, CNS Drugs.

[12]  J. Reginster,et al.  Osteoporosis in patients taking selective serotonin reuptake inhibitors: a focus on fracture outcome , 2015, Endocrine.

[13]  M. Humphrey,et al.  Medication-induced osteoporosis: screening and treatment strategies , 2014, Therapeutic advances in musculoskeletal disease.

[14]  E. M. Lewiecki,et al.  Clinician’s Guide to Prevention and Treatment of Osteoporosis , 2014, Osteoporosis International.

[15]  B. Mulsant,et al.  Depression, Antidepressants, and Bone Health in Older Adults: A Systematic Review , 2014, Journal of the American Geriatrics Society.

[16]  N. Keating,et al.  Effectiveness of primary androgen-deprivation therapy for clinically localized prostate cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Abrahamowicz,et al.  Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS) , 2014, Osteoporosis International.

[18]  W. Busse,et al.  Glucocorticoid-induced osteoporosis: an update on effects and management. , 2013, The Journal of allergy and clinical immunology.

[19]  J. Bollerslev,et al.  Medicines and bone loss. , 2013, The Journal of clinical endocrinology and metabolism.

[20]  K. Rothman,et al.  Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture , 2013, Journal of Family Planning and Reproductive Health Care.

[21]  W. Powderly Osteoporosis and Bone Health in HIV , 2012, Current HIV/AIDS Reports.

[22]  R. Rizzoli,et al.  Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper , 2012, Osteoporosis International.

[23]  D. Goltzman LRP5, serotonin, and bone: Complexity, contradictions, and conundrums , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  C. Roux,et al.  Prospective one-year bone loss in treatment-naïve HIV+ men and women on single or multiple drug HIV therapies. , 2011, Bone.

[25]  T. Rachner,et al.  Osteoporosis: now and the future , 2011, The Lancet.

[26]  A. Kearns,et al.  Update on medications with adverse skeletal effects. , 2011, Mayo Clinic proceedings.

[27]  Y. Fujiwara,et al.  Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  G. Mazziotti,et al.  Drug-induced osteoporosis: mechanisms and clinical implications. , 2010, The American journal of medicine.

[29]  Tjeerd P van Staa,et al.  Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. , 2010, Bone.

[30]  J. Forbes,et al.  Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[31]  Eugene McCloskey,et al.  FRAX and its applications to clinical practice. , 2009, Bone.

[32]  E John Orav,et al.  Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. , 2009, Archives of internal medicine.

[33]  Jeannie Huanga,et al.  A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis , 2009, AIDS.

[34]  M. Secic,et al.  Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. , 2008, Fertility and sterility.

[35]  C. Cooper,et al.  Epidemiology of osteoporosis. , 2008, Best practice & research. Clinical endocrinology & metabolism.

[36]  T. Brown,et al.  Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. , 2008, The Journal of clinical endocrinology and metabolism.

[37]  D. Bauer,et al.  Single‐Point Assessment of Warfarin Use and Risk of Osteoporosis in Elderly Men , 2008, Journal of the American Geriatrics Society.

[38]  P. Vestergaard,et al.  Effect of Tamoxifen and Aromatase Inhibitors on the Risk of Fractures in Women with Breast Cancer , 2008, Calcified Tissue International.

[39]  C. Roux,et al.  Drug-induced osteoporosis: Beyond glucocorticoids , 2008, Current rheumatology reports.

[40]  B. Biondi,et al.  The clinical significance of subclinical thyroid dysfunction. , 2008, Endocrine reviews.

[41]  M.N. Khan,et al.  Cancer treatment–related bone loss: a review and synthesis of the literature , 2008, Current oncology.

[42]  P. Delmas,et al.  Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. , 2007, Bone.

[43]  J. Reginster,et al.  Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club , 2007, Osteoporosis International.

[44]  P. Kantoff,et al.  Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  E. Perez,et al.  Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  S. Cawthorn,et al.  Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. , 2007, The Lancet. Oncology.

[47]  J. Richards,et al.  Effect of selective serotonin reuptake inhibitors on the risk of fracture. , 2007, Archives of internal medicine.

[48]  Yu-Xiao Yang,et al.  Long-term proton pump inhibitor therapy and risk of hip fracture. , 2006, JAMA.

[49]  T. Brown,et al.  Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review , 2006, AIDS.

[50]  T. Guise,et al.  Bone loss and fracture risk associated with cancer therapy. , 2006, The oncologist.

[51]  J. Ma,et al.  Effects of alendronate on bone mineral density in men with prostate cancer treated with androgen deprivation therapy. , 2006, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[52]  P. Vestergaard,et al.  Proton Pump Inhibitors, Histamine H2 Receptor Antagonists, and Other Antacid Medications and the Risk of Fracture , 2006, Calcified Tissue International.

[53]  D. Scholes,et al.  Depot medroxyprogesterone acetate and bone mineral density in adolescents--the Black Box Warning: a Position Paper of the Society for Adolescent Medicine. , 2006, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[54]  P. Vestergaard,et al.  Fracture risk associated with the use of morphine and opiates , 2006, Journal of internal medicine.

[55]  N. Franceschini,et al.  Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures , 2006, Clinical Rheumatology.

[56]  S. Gökben,et al.  Bone Mineral Status in Pediatric Outpatients on Antiepileptic Drug Monotherapy , 2006, Journal of child neurology.

[57]  P. Vestergaard,et al.  Fracture risk in patients treated with loop diuretics , 2006, Journal of internal medicine.

[58]  P. Vestergaard Epilepsy, osteoporosis and fracture risk – a meta‐analysis , 2005, Acta neurologica Scandinavica.

[59]  P. Vestergaard,et al.  Loop Diuretics Increase Bone Turnover and Decrease BMD in Osteopenic Postmenopausal Women: Results From a Randomized Controlled Study With Bumetanide , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[60]  C. Cooper,et al.  Use of Oral Corticosteroids and Risk of Fractures , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[61]  P. Tebas,et al.  Alendronate, Vitamin D, and Calcium for the Treatment of Osteopenia/Osteoporosis Associated With HIV Infection , 2005, Journal of acquired immune deficiency syndromes.

[62]  S. Hoerstrup,et al.  Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra®) on human osteoblasts in vitro , 2005, The British journal of surgery.

[63]  J. Goodwin,et al.  Risk of fracture after androgen deprivation for prostate cancer. , 2005, The New England journal of medicine.

[64]  J. Cuzick,et al.  Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer , 2005, The Lancet.

[65]  G. Canonica,et al.  Antihistamines: do they work? Further well‐controlled trials involving larger samples are needed , 2004, Allergy.

[66]  C. Higano,et al.  Osteoporosis in men with prostate carcinoma receiving androgen‐deprivation therapy , 2004, Cancer.

[67]  Stanley B. Cohen,et al.  Oral glucocorticoid use is associated with an increased risk of fracture , 2004, Osteoporosis International.

[68]  M. Drezner Treatment of anticonvulsant drug-induced bone disease , 2004, Epilepsy & Behavior.

[69]  Liam Smeeth,et al.  Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. , 2003, American journal of epidemiology.

[70]  P. J. Bowman,et al.  Central nervous system active medications and risk for fractures in older women. , 2003, Archives of internal medicine.

[71]  J. Body Zoledronic acid: an advance in tumour bone disease therapy and a new hope for osteoporosis , 2003, Expert opinion on pharmacotherapy.

[72]  C. Cooper,et al.  The Epidemiology of Corticosteroid-Induced Osteoporosis: a Meta-analysis , 2002, Osteoporosis International.

[73]  P. J. Bowman,et al.  Central Nervous System–Active Medications and Risk for Falls in Older Women , 2002, Journal of the American Geriatrics Society.

[74]  E. Miller,et al.  Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. , 2002, The Journal of clinical endocrinology and metabolism.

[75]  T. Tomson,et al.  Risk of Extremity Fractures in Adult Outpatients with Epilepsy , 2002, Epilepsia.

[76]  D. Kounali,et al.  Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density. , 2002, Rheumatology.

[77]  K. Saag Glucocorticoid use in rheumatoid arthritis , 2002, Current rheumatology reports.

[78]  W. Spain,et al.  Antiepileptic drug-induced bone loss in young male patients who have seizures. , 2002, Archives of neurology.

[79]  J. Franklyn,et al.  Levothyroxine treatment and occurrence of fracture of the hip. , 2002, Archives of internal medicine.

[80]  P. Kantoff,et al.  Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. , 2001, The New England journal of medicine.

[81]  D. Bauer,et al.  Risk for Fracture in Women with Low Serum Levels of Thyroid-Stimulating Hormone , 2001, Annals of Internal Medicine.

[82]  G. Otto,et al.  Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study , 2001, The Lancet.

[83]  C. Cooper,et al.  Use of Oral Corticosteroids and Risk of Fractures , 2000 .

[84]  P. Caraballo,et al.  Long-term use of oral anticoagulants and the risk of fracture. , 1999, Archives of internal medicine.

[85]  M. Dam,et al.  Fracture risk is increased in epilepsy , 1999, Acta neurologica Scandinavica.

[86]  S. Cummings,et al.  Warfarin Use and Risk for Osteoporosis in Elderly Women , 1998, Annals of Internal Medicine.

[87]  D. Sandeman,et al.  Effect of replacement doses of thyroxine on bone mineral density , 1998, Clinical endocrinology.

[88]  D. Bauer,et al.  Low thyrotropin levels are not associated with bone loss in older women: a prospective study. , 1997, The Journal of clinical endocrinology and metabolism.

[89]  P. Czernichow,et al.  Bone mineral density and metabolism in children with congenital hypothyroidism after prolonged l‐thyroxine therapy , 1997, Acta paediatrica.

[90]  S. Cummings,et al.  Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. , 1995, The New England journal of medicine.

[91]  H. Cushing The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. , 1994, Obesity research.

[92]  C. Marcocci,et al.  Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women. , 1994, The Journal of clinical endocrinology and metabolism.

[93]  A. Galløe,et al.  Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. , 1994, European journal of endocrinology.

[94]  N. Waugh,et al.  Morbidity in patients on l‐thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH , 1992, Clinical endocrinology.

[95]  J. Franklyn,et al.  Long-term thyroxine treatment and bone mineral density , 1992, The Lancet.

[96]  A. Maurer,et al.  Bone mineral density in postmenopausal women treated with L-thyroxine. , 1991, The American journal of medicine.

[97]  M. de Vernejoul,et al.  Cyclosporin-A in vitro decreases bone resorption, osteoclast formation, and the fusion of cells of the monocyte-macrophage lineage. , 1991, Endocrinology.

[98]  L. Sokoll,et al.  Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. , 1990, Annals of internal medicine.

[99]  L. Braverman,et al.  Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women. , 1988, JAMA.

[100]  G. Daniels,et al.  Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine. , 1987, The American journal of medicine.

[101]  S. P. Nielsen,et al.  SPINAL BONE MINERAL CONTENT IN MYXOEDEMA AND THYROTOXICOSIS. EFFECTS OF THYROID HORMONE(S) AND ANTITHYROID TREATMENT , 1983, Clinical endocrinology.

[102]  P. Price,et al.  Effects of warfarin on bone. Studies on the vitamin K-dependent protein of rat bone. , 1981, The Journal of biological chemistry.

[103]  F. Albright,et al.  POSTMENOPAUSAL OSTEOPOROSIS: ITS CLINICAL FEATURES , 1941 .

[104]  P. Camacho,et al.  Secondary causes of osteoporosis. , 2013, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[105]  V. Rabenda,et al.  Relationship between use of antidepressants and risk of fractures: a meta-analysis , 2012, Osteoporosis International.

[106]  M. Crowell,et al.  Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case–control studies , 2011, Osteoporosis International.

[107]  S. Warden,et al.  Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management? , 2010, Bone.

[108]  P. Hadji Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. , 2009, Critical reviews in oncology/hematology.

[109]  D. Felsenberg,et al.  Increase in Vertebral Fracture Risk in Postmenopausal Women Using Omeprazole , 2008, Calcified Tissue International.

[110]  M. Butcher,et al.  The effects of heparin and low molecular weight heparins on bone. , 2008, Thrombosis research.

[111]  H. Morris,et al.  Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. , 2002, Annual review of nutrition.

[112]  S. Epstein,et al.  Drug-Induced Bone Loss , 2000, Osteoporosis International.

[113]  M. Korpela [Methotrexate in the treatment of rheumatoid arthritis]. , 1996, Duodecim; laaketieteellinen aikakauskirja.

[114]  T. Diamond,et al.  Thyrotoxic Bone Disease in Women: A Potentially Reversible Disorder , 1994, Annals of Internal Medicine.