Osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to increased risk of fractures. The most common fractures are distal forearm, spine and hip fractures (HF). Catalonia is the region with the highest incidence of HF in Spain.1 According to the recorded minimum set of hospitalization database (MDS) of 2008,2 the fracture rate was 74.2 cases per 10,000 in persons over 64 years of age. HF usually occurs in older people and causes major economic costs and an even greater loss of quality of life.3 The diagnosis of osteoporosis can be performed by densitometry which should be performed only in those who have risk factors for osteoporosis. Among the different existing criteria, we selected the criteria proposed by the Agency of Information, Evaluation and Quality in Health in Catalonia (AIEHQC) collected in Table 1.4 These criteria were developed as a proposal of the Department of Health and are directed at health care professionals in our community. Alendronate is the drug of choice for osteoporosis and is effective in preventing vertebral and nonvertebral fractures, especially in women aged 70 years or older at high risk of fracture. The relative risk (RR) of HF in postmenopausal women after treatment with this bisphosphonate, with calcium and vitamin D (Ca+ DV), is 0.61 (level of evidence 1++ as indicated in a recent systematic review5). Treatment with bisphosphonates should be maintained for a minimum of about 5 years, stretching up to 7–10 years. Systematic review of economic studies conducted by García-Ruiz et al.5 shows that drug treatment of osteoporosis, especially with alendronate, is cost-effective for people with major risk factors: higher age, low bone density and a history of previous fractures. It is currently difficult to clearly define what is the cutoff age at which treatment should be started. Because drugs for treating osteoporosis can reduce the incidence of HF, the objective of this study was to determine the rate of HF in Catalonia and to determine whether primary drug prevention with alendronate for HF can be a measure implemented in our public health system based on cost-utility criteria, and which would counteract the diseases’ budgetary impact.

In the cost-utility analysis we compared 2 alternatives: the current strategy of “no prevention” versus the alternative “intervention” based on drug prevention in women aged 64 years or older diagnosed with osteoporosis by densitometry. A societal perspective was adopted and the time horizons considered were 20 and 10 years. We used a reduction rate of 5%. In the description of the budgetary impact we adopted the payer's perspective.

Base Case and Uncertainty Analysis

The analysis was conducted in the following age groups: 65–69 years, 70–74 years and 75–79 years of age. For the base case we calculated a 100% compliance and a fracture risk reduction of 40% for the first year, with persistence of the effect during the 10 years of treatment. An example of a decision tree is presented in Fig. 1. In the uncertainty analysis we have considered the following scenarios:

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  A decrease in compliance to 60%.

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  A 15% reduction of the protective effect of alendronate at 10 years.

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  Both effects.

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  The administration of alendronate for 7 years with a fracture risk reduction of 15% in 10 and 20 years.

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  A reduction rate of 3%.

Fig. 1.

Decision tree in women aged 65–69. Social perspective. 20-year time horizon.

(0.28MB).

Clinical Variables and Quality of LifePrevalence of Osteoporosis and Hip Fracture Incidence

The prevalence of osteoporosis in the Spanish female population, measured by axial densitometry,6 and the incidence of HF are shown in Table 2. Among women over 64 years of age with osteoporosis, the fracture RR is 1.7 (95% CI, 1.4–2.2).7 The distribution of HF between osteoporotic and non-osteoporotic women (Table 2) was calculated using the following formulas:

Table 2.

Prevalence of Osteoporosis by Axial Densitometry as Determined in Spanish Women; Incidence of HF in Women (2009) Based on Hospital Admission Records; Risk of HF in Women ≥65 Years at 10 and 20 Years and Estimated HF Distribution in Osteoporotic and Nonosteoporotic Women (Adopting an RR of 1.7).

Age	Prevalence of Osteoporosis in Women (%)a	Incidence of HF in Women (per 100)b	Risk of HF at 10 Years (%)c	Risk of HF at 20 Years (%)c	Estimated Incidence of HF in Osteoporotic Women at 20 Years (per 100)d	Estimated Incidence of HF in Nonosteoporotic Women at 20 Years (per 100)d
65–69	24.3	0.14	1.08	4.91	3.0	1.9
70–74	40.0	0.24	2.26	7.87	5.0	2.9
75–79	40.0	0.70	4.53	10.20	6.4	3.8
80–84	–	1.33	6.99	9.57	6.1	3.5
85–89	–	2.56	8.35	8.35	–	–
>90	–	3.26	5.94	5.94	–	–

a

Source: Diaz Curiel et al.6

b

Data obtained from hospital admission records.2

c

Data calculated with the Cutler–Ederer formula.8

d

Own calculations.

As I OP the incidence in women with osteoporosis and I no incidence of OP in osteoporotic women.

Risk of Hip Fracture

The likelihood of having a HF in the next 10–20 years (Table 2) was calculated with the Cutler–Ederer8 formula:

As the incidence Ia and In are the period of the incidence in the period n.

Indication of Densitometry

According to Roig-Vilaseca et al.,9 densitometry was indicated in 63.6% of women aged 65 years or older who attended primary health care centers if the criteria proposed by the AIEHQC were adopted.

Mortality

In addition to in-hospital mortality, in the first year after the fracture the mortality rate increased to 30%.10 However, in our model it is assumed that after the first year, the mortality rate is the same as the corresponding age group according to the Register of Deaths in Cataluña.11

Loss of Personal Autonomy (State Dependence)

About 50% of patients with HF have important disability.12 We adopted the figure of 45% found in one Barcelona13 study and 30% for a long-term3 situation.

Utility

To calculate the adjusted quality of life years (QALYs), the values used were taken from a recent review,14 i.e. 0.797 for the first year after the fracture and 0.899 for the following years. The usefulness in those that have failed to present a fracture is considered to be 1, regardless of age group, to compare changes in QALYs due only to the intervention. We used a reduction rate of 5%.

Drug prevention of HF is more efficient and cheaper than the option of doing nothing in the female population over 64 years, from a social and long-term perspective (20 years). Adopting the social22,23 perspective is based on the need to ensure that the use and distribution of public resources is done efficiently and with reasoned and transparent criteria. This justifies the use of QALYs as the unit of measure. The incorporation of the costs associated with a state of dependence due to FC can multiply the cost of HF 4, while a preventive policy proposal allows a saving of between 766.7 and € 2711.1 per QALY gained, depending on the age group. The incorporation of these costs has previously justified the application of some health policies in Catalonia for the acute care of stroke.24,25 In the 10-year time horizon, the intervention is effective but more expensive in the three age groups, although the costs obtained per QALY (13,881 for the 65–69 year group, 10,126 for the 70–74 group and 1988 the 75–79 year group) are within the recommended range of values. Moreover, the cost per QALY, especially in those aged 75–79, is not far from the values of other procedures prioritized in Catalonia, such as knee replacement surgery (€ 1353.5/QALY) or the hip replacement surgery (€ 8419.4/QALY values of 2010).26 The results are similar to those of other studies of cost-effectiveness. The cost per QALY gained in Germany from the strategy of screening and treatment of osteoporosis with alendronate27 was highest in women 60–70 years of age (€ 16589/QALY), reaching up to € 2337/QALY in the group of 80–89 years. The study by Kanis et al.28 demonstrated that primary prevention is cost-effective in women aged 50 years, lowering the cost of QALY progressively from age 60 and remaining dominant in the ≥80 years of age group. The proposed intervention involves nearly a 31% increase in current spending, but would not involve more than 0.5% of the total drug budget of the public insurer. Both the low cost per QALY as well as its small budgetary impact could justify the introduction of this preventive intervention in the 75–79 years of age group of women. The introduction of this measure, to be feasible, should be managed from primary care, as would be the appropriateness of prescribing bisphosphonates to the target population, avoiding unwarranted treatments. One limitation of the study is the criterion for the selection of persons at risk of osteoporosis. Shortly after the completion of our study, a publication appeared, which predicted that the positive predictive value of AIEHQC criteria for low bone density is 58.97% for women over 65 years of age, while the negative predictive value is high.29 The likelihood of osteoporosis that we have adopted is the same in the group with densitometry than in the group without; therefore overestimating fractures in the group without making densitometry analysis results are more robust. The upcoming availability of screening tools based on the absolute risk of osteoporotic fracture, and validated in our population, will improve the efficiency of the preventive strategy. In this sense, the FRAX® index (available in http://www.shef.ac.uk/FRAX/) which helps calculate the risk of fracture, may be an easily performed and useful tool.30 Another methodological limitation is the simplicity of the analysis employed, mainly based on point estimates of five-year age groups, the assumption of a linear increase (not exponential) of HF risk and uncertainty management through univariate sensitivity. However, it is assumed that the introduction of an exponential risk, the risk of a HF and transitional probabilities associated with age, would result in a greater number of fractures and greater cost-utility of preventive policy than has been analyzed. In summary, primary prevention of HF with alendronate plus Ca+ and vitamin D in women ≥65 years of age with osteoporosis is an intervention that has a long-term cost-utility (time horizon of 20 years). Within 10 years, the intervention in the group of women 75–79 years shows annual savings that reach 7.4 million euros on average, taking into account the total costs. The measure in that age group would have a budgetary impact on the public insurer.

Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation.

Confidentiality of Data. The authors declare that no patient data appears in this article.

Right to privacy and informed consent. The authors declare that no patient data appears in this article.

Mary J. Antonio Pueyo and J. Garcia-Ruiz developed the study design, analyzed the data and drafted the manuscript. Marta Larrosa Xavier Surís contributed to the idea of the project and the manuscript.

The authors declare no conflict of interest.