Musculoskeletal Adverse Drug Reactions: A Review of Literature and Data from ADR Spontaneous Reporting Databases

Abstract

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.

MiR-367 negatively regulates apoptosis induced by adriamycin in osteosarcoma cells by targeting KLF4

“…Our data also demonstrated that miR-367 was involved in ADR-induced apoptosis in OS cells. ADR is a kind of chemotherapeutic drug applied in kinds of malignant cancers [27] , [28] . ADR induced OS cells apoptosis, meanwhile, decreased the expression of miR-367.…”

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

“…Recently discovered deleterious effects of drugs on the ECM are tendinopathies associated with the use of statins (Marie et al, 2008) and fluoroquinolones (Conforti et al, 2007). Furthermore, skeletal consequences (particularly increased risk of bone fractures in the appendicular skeleton in women with type 2 diabetes, caused by thiazolidinediones, an antidiabetic drug class) has been noticed (Grey, 2008).…”

Factors Associated with Serious Adverse Reactions to Cholinesterase Inhibitors

“…These differences in the type of ADRs for conventional and atypical antipsychotics are globally consistent with results from the literature. [23][24][25][26][27][28][29][30] The association of antihypertensive drugs with SADRs seemed to be more important for autonomic nervous and vascular extra-cardiac ADRs than for other types of ADRs, which was not surprising as both these categories include hypotension ADRs. Even so, the use of antihypertensive drugs was associated with a 2-fold increase in the rate of reporting of CNS, gastrointestinal and heart rate and rhythm SADRs, very similar to the global increase in the risk of seriousness estimated for all ADRs in antihypertensive drug users.…”