Table 2.

Summary of characteristics of pharmacological agents for treating osteoporosis in clinical trials’ studies

Drugs class	Medication	Route of administration	Evidences of main effect		Ref.
			Increase in BMD	Decrease in fracture risk
FDA/EU Approved
Antiresorptive	BPs
	Alendronate	PO	Spine 6.2%, hip 4.1%, LS 5.4%, FN 1.6%,	Vertebral 47%, hip 51%, non-vertebral 16%	[1, 33, 37]
	Risedronate	PO	Trochanter 3.3%	Vertebral 36%, non-vertebral 27%, hip 40%	[1, 37]
	Ibandronate	PO/IV	Nearly 6% for LS & hip	Vertebral 50%, Non-vertebral 30-40%	[1, 22, 34–37]
	Zoledronic acid	IV	LS 3.2%, FN 24%	Vertebral 70%, non-vertebral 25% (including hip 40%)	[37, 38]
	Clodronate	PO/IM/IV	LS 3.7%, hip 1.3%	Vertebral 43%, non-vertebral 33%	[22]
	Denosumab	SC	LS 9.2-18.4%, hip 4-8.3%	Vertebral 68%, hip 40%, non-vertebral 20%	[45, 46]
	Estrogen Replacement (ERT, HRT)	PO	LS 7.6%, hip 4.5%	ERT: Vertebral 38%, hip 39% HRT: Vertebral 35%, hip 33%, wrist 29%	[22, 52, 53]
	SERMs
	Raloxifene	PO	LS 1.8%, hip 2.1%	Vertebral 35-43%, non-vertebral 10%	[22, 48, 57]
	Bazedoxifene	PO	LS 2.2-2.7%, hip (-1.15)-1.5%	(dose dependent) Vertebral 37-42%, non-vertebral no effect to 44-50% reduction	[56, 59, 60]
	Bazedoxifene+ conjugated estrogen	PO	LS 0.5-1.6%, hip 0.5-1.5%	NA	[62]
	Tamoxifene	PO	LS 1.2%	Overall 32% (hip 32%, spine 25%, radius 31%)	[63]
	Lasofoxifene	PO	LS 1.8-3.0%, hip 1.3-1.9%	(dose dependent) Vertebral 31-42%, non-vertebral 22-24%, no effect on hip fracture	[64, 66]
	Arzoxifene	PO	LS 2.75-2.9%, hip 1.53%	Vertebral 41%, no reduced non-vertebral	[67, 68]
	Calcitonin	Nasal spray/SC/IM	LS 1-1.5%	Vertebral 60%	[55]
Anabolic agents	PTH peptides
	Teriparatide	SC	Spine 8.6-13%, FN 3.5-6%	Vertebral 65-69%, non-vertebral 53%	[6, 55, 72, 73]
	PTH 1-84	SC	LS 6.9%, FN 2.5%	Vertebral 60%	[11, 73]
Newer Agents (awaiting FDA/EU approval)
Antiresorptive	Cathepsin k inhibitors
	Odanacatib	PO	Spine 11.9%, total hip 8.5%, FN 9.8%	Hip 47%, non-vertebral 23%, clinical vertebral 72%	[71, 76]
	ONO-5334	PO	Spine 3.7-5.1%, total hip 3%, FN 2.6%	NA	[78]
	Strontium	PO	Dose dependent: LS 2.39-5.44%, FN 2.52-8.25%, total hip 1.02-8.25%	Vertebral 37-40%, non-vertebral 13%, hip 5%	[81, 82]
Anabolic agents	Anti-sclerostin antibodies
	Romosozumab	SC	Dose dependent: LS 5.4-11.3%, total hip 4.1%, FN 3.7%	NA	[84]
	Blosozumab	SC/IV	Dose dependent: spine 8.4-17.0%, total hip 2.1-6.3%, FN 2.7-6.3%	NA	[85]
Combination therapy
Antiresorptive and anabolic agents	BPs + PTH
	Alendronate + Teriparatide	PO/SC	LS 14.8% vs. 18.1% by PTH/ 7.9% by BPs, total hip without differences	NA	[73]
	Risedronate + Teriparatide	PO/SC	Total hip 3.9% vs. 0.3% by PTH/ 0.8% by BPs, FN 8.4% vs. 3.9% by PTH/ 0.5% by BPs	NA	[73, 93]
	Zoledronic acid + Teriparatide	IV/SC	LS 7.5% vs. 7.0% by PTH/ 4.4% by BPs, total hip 2.3% vs. 1.1% by PTH / 2.2% by BPs	NA	[93]
	Denosumab + Teriparatide	SC/SC	LS 9.1% vs. 6.2% by PTH/ 5.5% by denosumab, total hip 4.9% vs. 0.7% by PTH/ 2.5% by denosumab, FN 4.2% vs. 0.8% by PTH/ 2.1% by denosumab	NA	[94]
	SERMs+ Teriparatide Raloxifene + Teriparatide	PO/SC	LS 6.2% vs. 5.2% by PTH, total hip 2.3% vs. 0.8% by PTH, FN 2.2% vs. 1.0% by PTH	NA	[57]
Antiresorptives	BPs+ HRT
	Etidronate + Estrogen	PO/PO	LS 10.4% vs.7.0% by HRT, hip 7.0% vs. 4.8% by HRT	NA	[95]
	Alendronate + HRT	PO/PO	LS 10.1% vs. 4.0% by HRT, FN 4.0% vs. 2.0% by HRT	NA	[35, 96]
	Risedronate + HRT	PO/PO	LS 5.2% vs. 4.6% by HRT, FN 2.7% vs. 1.8% by HRT	NA	[35]
	BPs+ SERMs Alendronate + Raloxifene	PO/PO	LS 5.3% vs. 4.3% by BPs/ 2.1% by raloxifene, FN 3.7% vs. 2.7% by BPs/ 1.7% by raloxifene,	NA	[57, 95]

Legend: BPs Bisphosphonates, FDA Food and Drug Administration, EU Europe, PO oral route, IV intravenous, SC subcutaneous, IM intramuscular, BMD bone mineral density, LS lumbar spine, FN femoral neck, GI gastrointestinal, HRT hormone replacement therapy, SERMs selective estrogen receptor modulators, AF arterial fibrillation, NA no evidence available