Table 2

Therapeutic agents available for osteoporosis, mode of action and fracture efficacy

	Mechanism of action	Fracture efficacy
Bisphosphonate (etidronate, ibandronate, alendronate, risedronate, zoledronate)	Antiresorptive: Reduce rate of bone turn-over and maintain or improve skeletal architecture. Inhibit farnesyl pyrophosphate synthase, resulting in reduced resorptive activity of osteoclasts and accelerated apoptosis. Rank order of potency is zoledronate > risedronate > ibandronate > alendronate.	Reduce vertebral fractures by 50–70%, non-vertebral fractures by 30% and hip fractures by 40%^* Based on bone turnover markers, maximum effect in 3 to 6 months. Effect on clinical vertebral fractures and non-vertebral fractures at 6–36 months depending on agent used (6 months for risedronate, 12–24 months for alendronate and 36 months for zoledronate based on pooled, post hoc analyses.
Selective Estrogen Receptor Modulator (SERM): for example Raloxifene	Inhibit bone resorption.	Reduce vertebral fracture by 35% with no decrease in non-vertebral and hip fracture in a meta-analysis.
Recombinant Human Parathyroid Hormone (PTH)	Anabolic: stimulates bone formation by reducing osteoblastic apoptosis and increasing osteoblast numbers and differentiation.	Reduces vertebral and non-vertebral fractures. Decrease vertebral fractures by 65% and non-vertebral by 54%.
Strontium Ranelate	Inhibit bone resorption and increase bone formation	Reduce vertebral fractures by 40%, and to a lesser extent non-vertebral fractures by 16% in meta-analysis. Decreased hip fracture by 36% in post hoc subgroup analysis in women aged 74 years or older.
Tibolone	Synthetic steroid with oestrogenic, androgenic, and progestagenic properties.	Reduce vertebral fractures by 45% and non-vertebral by 26% in postmenopausal women with improvements in BMD.
Testosterone	Increase bone formation.	Demonstrated to improve BMD in men with hypogonadism. Effects on fracture reduction unclear.
Denosumab	Blocking antibody to Receptor activator of NF–κβ Ligand (RANKL) which inhibits osteoclast formation and bone resorption.	Reduce vertebral fractures by 68%, non-vertebral by 20% and hip fractures by 40% in postmenopausal women, associated with increases in BMD and reciprocal decreases in markers of bone resorption

↵* Based on available evidence, only three of the bisphosphonates that is alendronate, risedronate and zoledronate reduce risk of hip fractures.
RCT, Randomized Control Trial; BMD, bone mineral density.