Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab

Figures & data

Table 1 Studies of denosumab in postmenopausal women with low bone mass

Study	Duration	Extent of bone disease	Total study size (plc) [60 mg/6 months]	Results
				Fractures	% BMD [% change versus plc]
McClung et al^Citation32	12 months	Osteopenia or osteoporosis (T-score < −1.8)	412 (46) [47]	No difference in the sum of denosumab groups compared with plc (3.8% versus 2.2%)*	LS: 4.6 [5.4] Hip: 3.6 [4.2]
Lewiecki et al^Citation84 (one-year extension of study by McClung et al)	24 months	Osteopenia or osteoporosis (T-score < −1.8)	412 (46) [47]	Increased clinical (6.7% versus 2.2%) and osteoporotic (3.8% versus 0.0%) fractures in the sum of denosumab groups compared with plc*	LS: 7.4 [8.6] Hip: 5.1 [NR]
Miller et al^Citation85 (2-year extension of study by Lewiecki et al)	48 months	Osteopenia or osteoporosis (T-score < −1.8)	412 (46) [231]	No difference in clinical (10.5% versus 10.9%) and osteoporotic (7.0% versus 8.7%) fractures compared with plc*	LS: 9.4–11.8 [11.8–14.2] Hip: 4.0–6.1 [7.5–9.6] Distal radius: 1.0–1.7 [5.7–6.4]
Miller et al^Citation14 (2-year extension of study by Miller et al in 2008)	72 months	Osteopenia or osteoporosis (T-score < −1.8)	124 [124]	4.5% (no plc group for comparison)*	LS: 13.3 Hip: 6.1 Distal radius: 1.9
Bone et al^Citation33	24 months	Osteopenia or osteoporosis	332 (166) [166]	Decreased vertebral (0% versus 0.6%) and nonvertebral (1% versus 4%) fractures compared with plc *	LS: 6.5 [7.1] Hip: 3.4 [4.5] Distal radius: 1.4 [3.5]
Cummings et al^Citation31 (FREEDOM trial)	36 months	Osteoporosis (T-score ≤ −2.5)	7868 (3906) [3902]	New vertebral fractures: 2.3% versus 7.2% in the plc group (68% reduction, P < 0.0001) [at 12 months 61%, at 24 months 78% reduction] New nonvertebral fractures: 6.5% versus 8.0% in the plc group (20% reduction, P < 0.011) Hip fractures: 0.7% versus 1.2% in the plc group (40% reduction, P < 0.036)	LS: NR [9.2 (8.2–10.1)] Hip: NR [6.0 (5.2–6.7)]
Papapoulos et al^Citation30 (2-year extension of FREEDOM trial)	60 months	Osteoporosis (T-score ≤ −2.5)	2343 [2343]	New vertebral fractures: year incidence 1.4% versus 2.2% in the virtual plc New nonvertebral fractures: year incidence 1.1% versus 2.6% in the virtual plc	LS: 13.7 Hip: 7.0 Distal radius: 2.3
Brown et al^Citation13	12 months	Low bone mass (T-score ≤ −2)	1189 (594) [595]	No difference in overall (4.0% versus 3.2%, P = 0.54) and osteoporotic (3.0% versus 2.2%, P = 0.37) fractures compared with alendronate*	LS: 5.3 Hip: 3.5 Distal radius: 3.1

Note:

* Fractures reported as adverse events (not as endpoints of the study).

Abbreviations: plc, placebo; NR, not reported; BMD, bone mineral density (measured by dual energy x-ray absorptiometry); LS, lumbar spine; hip, total hip.

Table 2 Safety concerns in postmenopausal women with osteoporosis treated with denosumab

Suboptimal tissue specificity		Bone turnover oversuppression
SIR	Rare	Hypocalcemia	Rare
Infections: Urinary, upper respiratory, gastrointestinal tract, ear		ONJ*	Very rare
	Uncommon
	Rare
Rashes/dermatitis	Uncommon	Delayed fracture	Controversial
Eczema	Rare	healing
Cataracts	Uncommon	“Frozen bone”	Controversial
Hypercholesterolemia	Uncommon	Atypical fragility	Controversial
Vascular calcifications	Controversial
Malignancies	Controversial

Notes: Classification was based on the following conventions: common (>10%), uncommon (1%–10%), rare (0.1%–1%), very rare (<0.1%) and controversial based on one-year event rates.

* Etiopathogenesis not fully elucidated yet and thus classification is conventional.

Abbreviations: SIR, serious infection risk, requiring hospitalization or resulting in death, (erysipelas, cellulitis); ONJ, osteonecrosis of the jaw.

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