Adverse Skeletal Effects of Drugs

There is an expanding list of drugs for which there are concerns regarding adverse skeletal effects. The effect of long-term use of glucocorticoid drugs to cause accelerated bone loss and increase the risk of fracture is well recognized. For some drugs (TKIs, calcineurin inhibitors and loop diuretics), the available data are inconsistent and/or do not support a definite adverse skeletal effect. Patients receiving these drugs can be managed in line with guidelines for the general population (See table). Other drugs (SSRIs, antipsychotic drugs, AEDs and PPIs) do not seem to affect bone metabolism or BMD, but there is evidence for increased fracture risk. However, the evidence is limited to observational data, and any relationship may be attributable either to nonbone effects of the drug or effects of the underlying condition to increase fracture rate. In these patients, evaluation for other risk factors for fracture and management of these risk factors should be considered. In a third group (depot MPA, chemotherapy and ART), there is evidence for increased bone loss and/or fracture, but the patient population is generally at low risk for fracture. In these cases, patients may require an assessment of risk, but will rarely require specific treatment for fracture risk reduction. In the last group (aromatase inhibitors, GnRH agonists and thiazolidinediones), there is evidence of increased risk of bone loss and/or fracture, and the drugs are more frequently prescribed to individuals at higher baseline fracture risk. Patients receiving these drugs require risk assessment and those at high risk of fracture should receive alternative treatments (or "add-back" HRT in the case of GnRH agonists) or, if necessary, specific treatment for osteoporosis.

Table:  Summary of management recommendations
Example drugs	Evidence for risk	Management recommendations
Tyrosine kinase inhibitors    Calcineurin inhibitors    Loop diuretics	No adverse  skeletal effect  or data  inconsistent	Manage as per general population
Selective serotonin re-uptake inhibitors (SSRIs)    Antipsychotics    Anti-epileptic drugs    Proton pump inhibitors	Evidence for increased fracture risk but fracture risk seems to relate to nonbone effects of the drug or effects of the underlying condition	Evaluate for other risk factors for fracture and manage these risk factors
Depot medroxyprogesterone acetate    Chemotherapy    Antiretroviral therapy	Evidence for increased bone loss and/or  fracture, but low risk population	Assessment of fracture risk, but will rarely require specific treatment
Aromatase inhibitors    Gonadotrophin hormone-releasing hormone agonists    Thiazolidinediones	Evidence for increased risk of bone loss and/or fracture, and the drugs are more frequently prescribed to individuals at higher baseline fracture risk	Assessment of fracture risk and those at high risk should receive alternative treatments and/or specific treatment for osteoporosis.

 The conclusions and table are from a longer article, “Adverse Skeletal Effects of Drugs – Beyond Glucocorticoids,” by Susannah O'Sullivan and Andrew Grey, Clin Endocrinol. 2015;82(1):12-22. 

http://www.medscape.com/viewarticle/837369_1