Stojadinovic A, Potter BK, Eberhardt J, et al: Development of a prognostic naïve Bayesian classifer for successful treatment of nonunions. J Bone Joint Surg Am 93: 187, 2011.
Silver JJ, Einhorn TA: Osteoporosis and aging: current update. Clin Orthop 316: 10, 1995.
Giannoudis P, Tzioupis C, Almalki T, et al: Fracture healing in osteoporotic fractures: is it really different? a basic science perspective. Injury 38 (suppl 1): S90, 2007.
Conforti A, Chimaulera C, Moretti U, et al: Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases. Curr Drug Safety 2: 47, 2007.
Mazziotti G, Canalis E, Giustina A: Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123: 877, 2010.
Guidance Document for the Preparation of Investigational Device Exemptions and Pre-market Approval Applications for Bone Growth Stimulator Devices, US Food and Drug Administration, Rockville, MD, 1988.
Miranda MA, Moon MS: “Treatment Strategy for Nonunions and Malunions,” in Surgical Treatment of Orthopaedic Trauma, edited by JP Stannard, AH Schmidt, PJ Kregor, Theime Medical Publishers, New York, 2007.
Bishop JA, Palanca AA, Bellino MJ, et al: Assessment of compromised fracture healing. J Am Acad Orthop Surg 20: 273, 2012.
Gaston MS, Simpson AH: Inhibition of fracture healing. J Bone Joint Surg Br 89: 1553, 2007.
Robinson CM, Court-Brown CM, McQueen MM, et al: Estimating the risk of nonunion following nonoperative treatment of a clavicular fracture. J Bone Joint Surg Am 86: 1359, 2004.
Perumal V, Roberts CS: Factors contributing to non-union of fractures. Curr Orthop 21: 258, 2007.
National Center for Health Statistics: Health, United States, 2010: With Special Feature on Death and Dying, National Center for Health Statistics, Hyattsville, MD, 2011.
World Health Organization: The Importance of Pharmacovigilance: Safety Monitoring of Medicinal Products, World Health Organization, Geneva, Switzerland, 2002. Available at: http://apps.who.int/medicinedocs/en/d/Js4893e/6.html. Accessed May 14, 2012.
Classen DC, Pestotnik SL, Evans RS, et al: Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 277: 301, 1997.
Pirmohamed M, Breckenridge AM, Kitteringham NR, et al: Adverse drug reactions. BMJ 316: 1295, 1998.
Kramer MS: Difficulties in assessing the adverse effects of drugs. Br J Clin Pharmacol 11: 105S, 1981.
Marks DH: “Evaluation of Medical Causation,” in Drug Injury: Liability, Analysis and Prevention, 2nd Ed, edited by JT O'Donnell, p 143, Lawyers & Judges Publishing Co Inc, Tucson, AZ, 2005.
Hutchinson TA, Lane DA: Assessing methods for causality assessment. J Clin Epidemiol 42: 5, 1989.
Hill AB: The environment and disease: association or causation? Proc R Soc Med 58: 293, 1965.
eHealthMe Web site. Available at: http://www.ehealthme.com. Accessed May 21, 2012.
IMS Institute for Healthcare Informatics: IMS Institute reports U.S. spending on medicines grew 2.3 percent in 2010, to $307.4 billion. Press release. Available at: http://www.imshealth.com/portal/site/imshealth/menuitem.a46c6d4df3db4b3d88f611019418c22a/?vgnextoid= 1648679328d6f210VgnVCM100000ed152ca2RCRD&vgnextchannel=41a67900b55a5110VgnVCM10000071812ca2RCRD&vgnextfmt=default. Published April 19, 2011. Accessed April 23, 2011.
Nishiya Y, Sugimoto S: Effects of various antihypertensive drugs on the function of osteoblast. Biol Pharm Bull 24: 628, 2001.
Sosa M, Saaveddra P, Gómez de Tejada MJ, et al: Beta-blocker use is associated with fragility fractures in postmenopausal women with coronary heart disease. Aging Clin Exp Res 23: 112, 2011.
Rejnmark L, Vestergaard P, Mosekilde L: Treatment with betablockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 24: 581, 2006.
Garrett IR, Mundy GR: The role of statins as potential targets for bone formation. Arthritis Res 4: 237, 2002.
Rejnmark L: Cardiovascular drugs and bone. Curr Drug Saf 3: 178, 2008.
Dale KM, Coleman CI, Henyan NM, et al: Statins and cancer risk: a meta-analysis. JAMA 295: 74, 2006.
Patil S, Holt G, Raby N, et al: Prospective, double blind, randomized, controlled trial of simvastatin in human fracture healing. J Orthop Res 27: 281, 2009.
Lindner T, Cockbain AJ, El Masry MA, et al: The effect of anticoagulant pharmacotherapy on fracture healing. Expert Opin Pharmacother 9: 1169, 2008.
Jamal SA, Browner WS, Bauer DC, et al: Warfarin use and risk for osteoporosis in elderly women: Study of Osteoporotic Fractures Research Group. Ann Intern Med 210: 829, 1998.
Simon RR, Beaudin SM, Johnston M, et al: Long-term treatment with sodium warfarin results in decreased femoral bone strength and cancellous bone volume in rats. Thromb Res 105: 353, 2002.
Wiens M, Etminan M, Gill SS, et al: Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med 260: 350, 2006.
Solomon DH, Mogun H, Garneau K, et al: Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res 26: 1561, 2011.
Rejnmark L, Vestergaard P, Mosekilde L: Reduce fracture risk in users of thiazide diuretics. Calcif Tissue Int 76: 167, 2005.
Rejnmark L, Vestergaard P, Mosekilde L: Fracture risk in patients treated with loop diuretics. J Intern Med 259: 117, 2006.
Goodman SB, Jiranek W, Petrow E, et al: The effects of medications on bone. J Am Acad Orthop Surg 15: 450, 2007.
Misra M, Papalostas GI, Kibanski A: Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 65: 1607, 2004.
Dore DD, Trivedi AN, Mor V, et al: Atypical antipsychotic use and risk of fracture in persons with parkinsonism. Mov Disord 24: 1941, 2009.
Vestergaard P, Rejnmark L, Mosekilde L: Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int 82: 92, 2008.
Vestergaard P, Rejnmark L, Mosekilde L: Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17: 807, 2006.
Vestergaard P: Changes in bone turnover, bone mineral and fracture risk induced by drugs used to treat epilepsy. Curr Drug Saf 3: 168, 2008.
Jetté N, Lix LM, Metge CJ, et al: Association of antiepileptic drugs with nontraumatic fractures: a population-based analysis. Arch Neurol 68: 107, 2001.
Lecka-Czernik B: Bone loss in diabetes: use of antidiabetic thiazolidediones and secondary osteoporosis. Curr Osteoporos Rep 8: 178, 2010.
Pountos I, Georgouli T, Blokhuis TJ, et al: Pharmacological agents and impairment of fracture healing: what is the evidence? Injury 39: 384, 2008.
Abu EO, Horner A, Kusec V, et al: The localization of the functional glucorticoid receptor alpha in human bone. J Clin Endocrinol Metab 85: 883, 2000.
Lafage-Proust MH, Boudignon B, Thomas T: Glucocorticoid-induced osteoporosis: pathophysiological data and recent treatments. Joint Bone Spine 70: 109, 2003.
Lakatos P: Thyroid hormones: beneficial or deleterious for bone? Calcif Tissue Int 73: 205, 2003.
Vuolteenaho K, Moilanen T, Moilanen E: Non-steroidal anti-inflammatory drugs cyclooxygenase-2 and the bone healing process. Basic Clin Pharmacol Toxicol 102: 10, 2008.
Giannoudis PV, MacDonald DA, Matthews SJ, et al: Nonunion of the femoral diaphysis: the influence of reaming and nonsteroidal anti-inflammatory drugs. J Bone Joint Surg Br 82: 655, 2000.
Dodwell ER, Latorre JG Parisini E, et al: NSAID exposure and risk of nonunion: a meta-analysis of case control and cohort studies. Calcif Tissue Int 87: 193, 2010.
Pountos I, Georgouli T, Calori GM, et al: Do nonsteroidal anti-inflammatory drugs affect bone healing? a critical analysis [published online January 4, 2012]. ScientificWorldJournal 2012. doi:.
Vestergaard P, Rejnmark L, Mosekilde L: Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 79: 76, 2006.
Van Wunnik BP, Weijers PH, van Helden SH, et al: Osteoporosis is not a risk factor for the development of nonunion: a cohort nested case-control study. Injury 42: 1491, 2011.
Recognizing the existence of adverse drug effects of frequently prescribed drugs can empower a clinician with knowledge to avoid dangerous adverse effects that may result in hazardous, negative patient outcomes on either fracture healing or bone health. Pharmacovigilance reports have described the influence of medications, allowing for bone health to be quite unpredictable.
First, mechanisms found in the medical literature of potential drug adverse effects regarding fracture healing are presented. Second, the 100 most frequently prescribed medications in 2010 are reviewed regarding adverse effects on fracture healing. These reported adverse effects are evaluated for medical causation. Last, a data table describing the 100 reviewed medications and their reported effects on fracture healing is provided.
The actual number of different medications in the review was 72. Reported drug adverse effects on bone and fracture healing occurred with 59 of the 72 drugs (81.9%). These adverse effects are either described as a definitive statement or represented by postmarketing case reports. Thirteen of the 72 review drugs (18.1%) did not have any description of the possible effects on bone health. A total of 301 cases reports describing delayed union, malunion, and nonunion of fractures represent 31 of the 72 medications reviewed (43.1%).
This review offers the health-care provider information regarding potential adverse drug effects on bone health. Empowered with this information, clinicians may assist their patients in maximizing pharmacologic outcomes by avoiding these reported harmful adverse effects.