Cost-effectiveness of treatment of women aged 70 years and older with both osteopenia and microstructural deterioration
Introduction
Advancing age is associated with bone fragility and an increased fracture risk [1]. The fracture burden is rising because longevity is increasing the number of older people in the community [2]. The term ‘osteoporosis’ is assigned to persons with bone mineral density (BMD) T-score of ≤−2.5 standardized deviations (SDs) below the premenopausal mean (1), but bone fragility is not confined to women with osteoporosis. Postmenopausal women with more modest deficits in BMD categorized as osteopenia, a BMD T-score between −1 and −2.5 SD, have a lower risk of fracture than women with osteoporosis, but they are not free of fracture risk [3].
Over 70% of all fragility fractures arise among the majority of postmenopausal women in the population with osteopenia [[3], [4], [5]]. This is similar to the burden of cardiovascular disease; most events arise from individuals with moderately hypertension or hyperlipidemia [6]. Thus, confining treatment to only women with osteoporosis fails to address the population burden of fractures.
Most fractures, particularly non-vertebral and hip fractures, which comprise over 70% of all fractures, occur in women over 70 years of age. Measurement of bone density forms part of the standard assessment of fracture risk in women presenting following a first fragility fracture or concerned about the possibility of a first fracture. However, uptake of therapy remains suboptimal, especially in women found to have osteopenia, even in the presence of a fragility fracture [7].
To curb this burden requires a strategy to identify and target postmenopausal women with osteopenia with bone fragility. Women with osteopenia at imminent risk (within 1–2 years) and intermediate risk (within 2–4 years) for fracture have bone fragility partly due to microstructural deterioration [[7], [8], [9], [10], [11]]. BMD does not capture this fragility because microstructural deterioration increases fragility disproportionately to the bone loss producing it and the modest BMD deficits of osteopenia [12].
These women can be identified by measuring microstructural deterioration using high resolution peripheral quantitative tomography (HRpQCT) and targeting them for therapy. We have quantified cortical and trabecular microstructural deterioration and expressed this deterioration as a structural fragility score. We reported using a threshold denoting severe structural deterioration captures a large proportion of women with osteopenia sustaining fractures before the event [3]. Treating women with osteopenia using zoledronate reduces fracture risk [13]. However, it is uncertain whether complementing a BMD measurement with additional measurement of the structural fragility score using HRpQCT to identify those at high risk with microstructural deterioration is cost-effective compared to current standard of care. We addressed this issue in the present study, adopting the perspective of the US healthcare system. We also evaluated and compared the economic outcomes of a ‘global approach of treating all women ≥70 years of age with osteopenia compared to current standard of care.
Section snippets
Model
A state-transition Markov model was developed in Microsoft Excel to simulate the progress of women aged ≥70 years with osteopenia, no previous fractures and a SFS of ≥70 at baseline [14]. The model comprised three health states: ‘Alive, no prior fracture’, ‘Alive, post fracture’ and ‘Dead’ (Fig. 1). ‘Fracture’ comprised major fragility fracture involving the hip, vertebra or wrist. All subjects began the simulation in the health state ‘Alive, no fracture’, and over yearly cycles, could develop
Results
The model predicted that in the Standard Care Group, 327 fractures (284 first and 43 recurrent) would have occurred over the 10-year time horizon among the 1000 subjects compared to 300 fractures (261 first and 39 recurrent) in the Intervention Group assessed using HRpQCT and treated based on finding SFS to be ≥70 units. Hence, targeting treatment based on the presence of severe microstructural deterioration prevented 27 fractures over the 10-year period, equating to a number needed to treat
Discussion
Measurement of severe microstructural deterioration identifies women aged ≥70 years with osteopenia at imminent risk for fracture [3]. Over 70% of the fracture burden in the community arises among women with osteopenia or normal BMD [[3], [4], [5],10]. The preliminary health economic analyses in that report [3], provided an indicative measure of cost-effectiveness using a simplified model structure and key data inputs with a modelled time horizon to five years. The parameters of the present
CRediT authorship contribution statement
D Liew: conceptualization, methology, software formal analysis, writing.
RD Chapurlat: investigation, resources, supervision, project administration, funding.
E Sornay-Rendu: investigation, resources, supervision, project administration.
Eric Lespessailles: investigation, resources, supervision, project administration.
Yu Peng: methodology, software, resources.
E Seeman: conceptualization, writing.
Declaration of competing interest
ES is a board member and shareholder in Straxcorp. YP is employee of Straxcorp.
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