Zoledronic acid: clinical utility and patient considerations in osteoporosis and low bone mass

Figures & data

Table 1 Indications for zoledronic acid based on selected published studies

Indication	Postmenopausal osteoporosis^Citation25		Post-hip fracture^Citation30		Glucocorticoid-induced Osteoporosis^Citation20,Citation29
Name of study	HORIZON-PFT		HORIZON-RFT		HORIZON-GIO
					Prevention	Treatment
Study type	Double-blind; randomized		Double-blind;randomized		Double-blind, randomized; non-inferiority
Control	Placebo		Placebo		Risedronate
Duration (yrs)	3		3		1
Number included	7,736		2,127		288	545
Age (yrs): mean/range	Placebo	73.0 ± 5.4	Placebo	74.6 ± 9.86	57.2 ± 15.1	53.0 ± 13.8
	Zoledronate	73.1 ± 5.34	Zoledronate	74.4 ± 9.48
Inclusion criteria	T ≤ −2.5 or T ≤ −1.5 and vertebral fx		Osteoporotic hip fx in the previous 3 months		Glucocorticoid therapy duration
					≤3 months	>3 months
End point	Fractures Bone mineral density Bone markers		Fractures Mortality		Bone mineral density Bone markers
Fracture risk reduction vs control	Hip fx	41%	New clinical fx 35%		N/A
	Vertebral (morph) fx	70%
	New vertebral fx	25%
BMD vs control	Total hip	6%	N/A		Lumbar vertebrae
	Femoral neck	5.1%			Zoledronate 2.6%	Zoledronate 4.1%
	Lumbar vertebrae	6.7%			Risedronate 0.6%	Risedronate 2.7%
Mortality	N/A		28%		N/A

Abbreviations: HORIZON, Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly; PFT, Pivotal Fracture Trial; RFT, Recurrent Fracture Trial; GIO, Glucocorticoid-Induced Osteoporosis; fx, fracture; LV, lumbar vertebrae; BMD, bone mineral density; N/A, not applicable.

Figure 1 Incidence of fractures during the 3-year study period.⁷ The primary end points – the incidence of morphometric vertebral fracture (Panel A) and the 3-year incidence of hip fracture (Panel B) – are shown for both groups. In Panel A, the 5675 patients in stratum 1 who were included in the analysis underwent radiography at baseline and at least once during follow up. Any missing data for earlier visits were imputed from later visits, and missing data for later visits were imputed from earlier visits. The total number of follow up radiographs were 5675 at 1 year, 5308 at 2 years, and 4969 at 3 years. Secondary end points – nonvertebral fracture (Panel C), any clinical fracture (Panel D), and clinical vertebral fracture (Panel E) – are also shown over a 3-year period. In panels B, C, D, and E, the number of subjects at 36 months is the number who had closeout visits on or after the start of the 36-month window for visits.

Reproduced with permission from Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–1822.²⁵ © 2007 Massachusetts Medical Society. All Rights Reserved.

Table 2 Indications for zoledronic acid, based on selected as yet unpublished studies

Indication	Men^Citation20,Citation33		Prevention^Citation20,Citation34,Citation35
Name of study	Unpublished		Unpublished
Study type	Non-inferiority; randomized		Double-blind; randomized
Control	Alendronate*		Placebo
Duration (yrs)	2		2
Number included	302		224		357
Age	Mean 64 years Range 25–86 years		≥45 years
Inclusion criteria			Osteopenia <5 yrs postmenopause		Osteopenia ≥5 yrs postmenopause
End point	Bone mineral density		Bone mineral density
Fracture risk Reduction vs control	N/A		N/A
BMD vs control	Zoledronate	6.1%	Zoledronate	LV – 4.0%	Zoledronate	LV – 4.8%
				Hip – 2.6%		Hip – 2.1%
	Alendronate	6.2%	Placebo	LV – 2.2%	Placebo	LV – 0.7%
				Hip – 2.1%		Hip – 1.0%
Mortality	N/A		N/A

* As cited by Piper³³ regarding the HORIZON study mentioned in Reclast²⁰ which does not name the active control.

Abbreviations: BMD, bone mineral density; LV, lumbar vertebrae; N/A not available.

Figure 2 Most common adverse events within 3 days after infusion in HORZON PFT and RFT. (Unpublished data. Study ZOL445H2301, Novartis Pharmaceuticals and Study CZOL446L2310, Novartis Pharmaceuticals).

Notes: HORIZON PFT, Health Outcomes and Reduced incidence with Zoledronic Acid Once Yearly. Pivotal Fracture Trial: RFT, Recurrent Fracture Trial.

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