The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland, Norway and the Netherlands

Figures & data

Figure 1.  Structural diagram of the cost-effectiveness model.

Table 1.  Efficacy values for the prevention of fragility fractures in postmenopausal women.

Intervention	Mean relative risk of fracture event (95% CI)
	Hip	Vertebra	Wrist	Proximal humerus
Zoledronic acid 5 mg14,28	0.59 (0.42–0.83)	0.30 (0.24–0.38)	0.81 (0.62–1.06)	0.58 (0.39–0.85)
Alendronate8,29	0.62 (0.40–0.98)	0.56 (0.46–0.68)	0.67 (0.34–1.31)	0.81 (0.68–0.97)
Risedronate8,29	0.74 (0.59–0.93)	0.61 (0.50–0.75)	0.68 (0.43–1.08)	0.76 (0.64–0.91)
Ibandronate30–32	1.00 (N/A)	0.38 (0.25–0.59)	1.00 (N/A)	1.00 (N/A)

CI, confidence interval; N/A, not applicable.

Table 2.  Annual direct costs for patients with osteoporosis.

Costs	Finland (€)	Norway (NOK)	The Netherlands (€)
Fracture-associated costs^a
Hip fracture	843933	119,792^b34	15,91235
Nursing home entry	43,971 impact cost; 41,172 annual cost33	577,706^c36,37	48,209 impact cost; 32,297 annual cost35,38
Death	843933	95,833^d	15,91235
Vertebra	1070 impact cost33; 353 annual cost39	20,672^b40	772235
Proximal humerus	1010 (aged 50–80 years)	16,958^e	315935
	1757 (aged >80 years)33
Wrist	918 (aged 50–80 years)	16,95834	106535
	2012 (aged >80 years)33
Drug costs^f,g
Zoledronic acid 5 mg^h	529.7339	3632.8041	428.92^i42
Generic alendronate	367.3039	663.5241	18.5042
Branded alendronate	546.7739	2765.7041	214.2442
Risedronate	458.6839	3115.4041	361.2742
Ibandronate (oral)	546.0039	3266.9041	353.2842
Ibandronate (IV)^h	1106.8639	4686.4041	891.8042
Other costs^a
Clinic visits	–^g	26043	–^j

^aThe same costs were assumed for all ages unless otherwise stated; costs were for 2006 for Finland and the Netherlands and 2007 for Norway (relevant exchange rate: NOK1 = €0.125). ^bAdjusted from source for inflation and exchange rates. ^cYearly nursing home cost (NOK634,370) corrected for normal living costs for the elderly (NOK56,664). ^dAssuming 80% of cost of hip fracture. ^eAssumed to be the same as wrist fracture. ^f2008 costs (relevant exchange rate: NOK1 = €0.122). ^gFor Finland, drug costs include one clinic visit per year for oral bisphosphonates, one visit (including infusion) for zoledronic acid 5 mg and four visits (including the costs of injection) for IV ibandronate; costs of clinic visits taken from Hujanen33. ^hIncludes cost for infusion, with the exception of IV ibandronate in the Netherlands. ⁱInfusion costs from the Institute for Medical Technology Assessment, the Netherlands; personal communication. ^jCosts of visits not included.

IV, intravenous.

Figure 2.  Cost effectiveness by age group for selected bisphosphonates compared with basic treatment in (a) Finland, (b) Norway and (c) the Netherlands. Negative values indicate dominance, i.e. better efficacy and lower cost. ICER, incremental cost-effectiveness ratio; IV, intravenous; QALY, quality-adjusted life-year.

Figure 3.  Cost effectiveness by age group for zoledronic acid 5 mg compared with selected bisphosphonates in (a) Finland, (b) Norway and (c) the Netherlands. Negative values indicate dominance, i.e. better efficacy and lower cost. ICER, incremental cost-effectiveness ratio; IV, intravenous; QALY, quality-adjusted life-year.

Table 3.  Sensitivity analyses: Incremental cost-effectiveness ratios for zoledronic acid 5 mg versus branded alendronate.

Scenario	Finland (€)	Norway (NOK)	The Netherlands (€)
Base case	25,287	Dominant	873
Reducing cost of alendronate by 50%	52,746	15,789	20,157
Restricting nursing home costs to 3 years	26,997	Dominant	1887
Patients with a lower T-score (−3.5)	22,734	Dominant	Dominant
50% reduction in long-term utility decrement for hip and vertebral fractures	28,063	Dominant	1477
PSA results*	57%	87%	79%

*Probability that cost effective at a threshold of €30,000 or NOK200,000.

PSA, probabilistic sensitivity analysis.

Table 4.  Sensitivity analyses: Incremental cost-effectiveness ratios for zoledronic acid 5 mg versus generic alendronate at different compliance rates for generic alendronate.

Age (years)	Compliance with generic alendronate
	100%	90%*	80%*
Finland (€)
50	30,258	11,216	4450
60	33,527	12,523	6756
70	21,419	6774	669
80	39,614	9709	2529
Norway (NOK)
50	396,574	126,744	10,179
60	363,009	50,511	12,286
70	166,726	−8370	−69,670
80	130,794	−281,242	−354,558
The Netherlands (€)
50	88,102	50,698	36,098
60	87,092	42,966	30,414
70	82,327	36,919	25,248
80	118,800	39,035	16,519

*A 90% level of patient compliance was calculated to give 70% of maximal drug efficacy in preventing fracture and 80% compliance to give 50% efficacy, as described by Siris et al.11.

Negative values indicate that zoledronic acid 5 mg was dominant, i.e. more effective, at a lower cost.

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

 PubMed Web of Science ®Google Scholar

Olson M, Brereton N, Huels J, et al. Comparison of the cost-effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in the UK setting. Poster POS8 presented at the annual European congress of the International Society for Pharmacoeconomics and Outcomes Research, Dublin, Ireland, 20-23 October, 2007

 Google Scholar

Stevenson M, Lloyd Jones M, De Nigris E, et al. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess 2005;9:1-160

 PubMed Web of Science ®Google Scholar

National Institute for Health and Clinical Excellence. Final Appraisal Determination: Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women. 2007. Available at: http://guidance.nice.org.uk/page.aspx?o=437523 [Last accessed December 2009]

 Google Scholar

Hujanen T. Terveydenhuollon yksikkökustannukset Suomessa vuonna 2001, Stakes Aiheita 1/2003. Available at: http://www.stakes.fi/verkkojulkaisut/muut/Aiheita1-2003.pdf [Last accessed September 2007]

 Google Scholar

Borgstrøm F, Zethraeus N, Johnell O, et al. Costs and quality of life associated with osteoporotic-related fractures in Sweden. Osteoporos Int 2006;17:637-650

 PubMed Web of Science ®Google Scholar

Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic, epidemiological review. Osteoporos Int 2009;20:1633-1650

 PubMed Web of Science ®Google Scholar

Klotzbuecher CM, Ross PD, Landsman PB, et al. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 2000;15:721-739

 PubMed Web of Science ®Google Scholar

KOSTRA. Korrigerte brutto driftsutg., pleie i institusjon, pr. kommunal plass. 2006. Available at: http://www.ssb.no/kostra [Last accessed December 2007]

 Google Scholar

Forbruksundersøkelsen 2003-2005. Available at: www.ssb.no/emner/05/02/fbu/tab-2006-09-11-01.html [Last accessed December 2007]

 Google Scholar

Meerding WJ, Mulder S, van Beeck EF. Incidence and costs of injuries in The Netherlands. Eur J Public Health 2006;16:272-278

 PubMedGoogle Scholar

Oostenbrink JB, Bouwmans CAM, Koopmanschap MA. Handleiding voor kostenonderzoek, methoden en standaard kostprijzen voor economische evaluaties in de gezondheidzorg. Geactualiseerde versie 2004. Diemen, The Netherlands: College voor zorgverzekeringen, 2004

 Google Scholar

SLD price database. Helsinki, Finland: Finnish Pharmaceutical Data Ltd, 2008

 Google Scholar

Stevenson MD, Davis SE, Kanis JA. The hospitalisation costs and out-patient costs of fragility fractures. Women's Health Med 2006;3:149-151

 Google Scholar

Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone 2004;35:375-382

 PubMed Web of Science ®Google Scholar

Seeman E, Compston J, Adachi J, et al. Non-compliance: the Achilles' heel of anti-fracture efficacy. Osteoporos Int 2007;18:711-719

 PubMed Web of Science ®Google Scholar

Norwegian Medicines Agency Database. 2008. Available at: http://www.legemiddelverket.no/custom/Preparatsok/prepSearch____80333.aspx [Last accessed July 2008]

 Google Scholar

Z-Index bv. Z-Index Taxe, December 2008

 Google Scholar

Den norske legeforening. Normaltariff of privat spesialistpraksis 2007-2008. Oslo, Norway: Den norske legeforening. 2007. Available at: http://www.legeforeningen.no/assets/Normaltariffen_2007.pdf [Last accessed December 2007]

 Google Scholar

Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 2006;81:1013-1022

 PubMed Web of Science ®Google Scholar