Table 6.

Drug classes associated with bone loss and/or fragility fractures

Drug class	Loss of BMD [81]	Increased fracture risk [81]	Literature review
Androgen deprivation therapy	Gonadotropin-releasing hormone agonists (GnRHs) are the most commonly used ADT. BMD declines by 2-5% during the first year of ADT.	The risk of hip and vertebral fractures increases to 20-50% after 5 years of ADT. Fracture risk correlates with age, rate of BMD loss and ADT exposure.	Bienz and Saad [82]
Anticoagulants	Long-term heparin use leads to loss of BMD. Up to 30% of heparin-treated pregnant women lose BMD.	2.2-3.6% of heparin-treated pregnant women sustain fractures. 15% of non-pregnant women long-term users sustain vertebral fractures.	Coppola et al [83]
Anticonvulsants	In epilepsy, ACs are associated with bone loss in men >65 years and postmenopausal women. Phenytoin has been associated with BMD loss in young women.	Meta-analysis has shown treatment with ACs to be associated with increased fracture risk, with a relative risk (RR) of 2.2. Fracture risk is dependent on duration and dose.	van der Kruijs et al [84]
Aromatase inhibitors	The annual rate of bone loss in women taking AIs is approx. 2.5% as compared to 1-2% for healthy postmenopausal women [85].	Women treated with AIs have a 30% higher fracture risk than age-matched healthy women. AI users sustain more peripheral fractures than hip or vertebral fractures [85].	Rizzoli et al [85]
Calcineurin inhibitors	The direct effect of CIs on BMD is not clear due to post-transplant GC use and compromised bone health before transplants.	Several studies suggest that CIs are associated with fragility fractures in a dose and duration dependent fashion.	Lan et al [86]
Glucocorticoids	While all recipients of GCs are at increased risk of bone loss, older men and postmenopausal women are at highest risk with GC doses of >20 mg daily.	30-50% of patients receiving GCs develop fractures. GC-induced osteocyte apoptosis leads to early increase in fracture risk prior to loss of BMD.	Whittier and Saag [87]
Medroxyprogesterone acetate	Depot MPA has been shown to reduce BMD by 2-8%. Bone loss is rapid during the first 2 years of treatment then stabilises.	Depot MPA is associated with a slight increase in fracture risk. More studies are needed to definitively assess the impact on fracture risk.	Lopez et al [88]
Proton pump inhibitors	There is no clear association between PPI use and loss of BMD. The mechanism by which PPIs increase fracture risk is unknown.	PPIs use is associated with a modest increase in fracture risk. Fracture risk appears to be related to duration of PPI use.	Lau et al [89]
Selective serotonin reuptake inhibitors	Small studies have found an association between SSRI use and bone loss. However, meta-analysis has reported SSRI-related fractures in the absence of bone loss.	Two meta-analyses have reported the adjusted odds ratio for fracture among SSRI users to be approx. 1.7. Fracture risk is dependent on dose and duration of SSRI treatment.	Rizzoli et al [90]
Thiazolidinediones	TZDs reduce bone formation through impairing differentiation of osteoblast precursors, and increase resorption through several mechanisms, resulting in bone loss.	Two meta-analyses have reported that TZDs significantly increase fracture incidence in women with Type 2 diabetes, but not in men. Notably, fracture risk is increased in young women without risk factors.	Napoli et al [91]