Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.
The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed.
Conforti
Anita
A
Department of Medicine and Public Health, Section of Pharmacology, University of Verona, Italy.
Chiamulera
Christian
C
Moretti
Ugo
U
Colcera
Sonia
S
Fumagalli
Guido
G
Leone
Roberto
R
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D016907:Adverse Drug Reaction Reporting Systems; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D016208:Databases, Factual; D004164:Diphosphonates / Q000009:adverse effects; D024841:Fluoroquinolones / Q000009:adverse effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects; D009140:Musculoskeletal Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D011358:Product Surveillance, Postmarketing; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D012176:Retinoids / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D000890:Anti-Infective Agents; D000925:Anticoagulants; D014150:Antipsychotic Agents; D004164:Diphosphonates; D024841:Fluoroquinolones; D000960:Hypolipidemic Agents; D054328:Proton Pump Inhibitors; D012176:Retinoids