Table 1.

Overview of typical osteoporotic medications and the effect on fracture risk and bone mineral density (BMD)

Medication	Indications*	Administration	Major trials reporting decreased fracture risk	Effect on BMD	Underlying mechanism of the effect medication on bone
Bisphosphonates	Treatment/prevention of osteoporosis in postmenopausal women, osteoporosis in men, glucocorticoid-induced osteoporosis, Paget disease of bone, hypercalcemia of malignancy, multiple myeloma, malignancies with bone metastasis	Tablets orally, oral solution, intravenous infusion	Fracture Intervention Trial [60, 61], Vertebral Efficacy with Risedronate Therapy (VERT) Multinational (VERT-MN) and VERT-North America (VERT-NA) [63, 64], Hip Intervention Program Study Group [65], Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial [66–68]	Increase	Inhibit osteoclasts, preventing them from bone resorption
Teriparatide	Treatment of osteoporosis in postmenopausal women, primary or hypogonadal osteoporosis in men, osteoporosis associated with sustained systemic glucocorticoid therapy in men and women, all at high risk for fracture	Subcutaneous	Effect of parathyroid hormone on fractures trial [78], VERtebral fracture treatment comparisons in Osteoporotic women (VERO) study [84]	Increase	Increases bone formation and resorption with net bone formation, bone quality improvements, and higher bone mass caused by effects of intermittently increased PTH levels
Abaloparatide	Treatment of osteoporosis in postmenopausal women at high risk for fracture	Subcutaneous	The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial and extensions [95–98]	Increase	Binds with high selectivity to the RG conformation of PTHR1, resulting in a shorter intracellular signaling response, which results in transient activation of PTHR1, causing a positive effect on bone formation
Denosumab	Treatment of osteoporosis in postmenopausal women, to increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer, to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer, all at high risk for fracture	Subcutaneous	Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial and extensions [104–108]	Increase	Binds RANKL, leading to inhibition of the formation, activation, and survival of the osteoclasts
Romosozumab	Treatment of osteoporosis in postmenopausal women at high risk for fracture or treatment of patients who have failed/are intolerant to other osteoporosis therapy	Subcutaneous	Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) [134–136], the Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk of Fracture (ARCH) [133]	Increase	Inhibits sclerostin, resulting in activation of the Wnt/β-catenin signaling pathway, causing an increase in the differentiation of osteoblast precursors and the bone formation by osteoblasts

*US Food and Drug Administration-approved indications. PTH = parathyroid hormone; PTHR1 = PTH receptor type 1; RANKL = receptor activator of nuclear factor kappa-Β ligand.