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The American Journal of Managed Care March 2020
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Validated Prediction of Imminent Risk of Fracture for Older Adults
Richard L. Sheer, BA; Richard L. Barron, MS; Lavanya Sudharshan, MS; and Margaret K. Pasquale, PhD

Validated Prediction of Imminent Risk of Fracture for Older Adults

Richard L. Sheer, BA; Richard L. Barron, MS; Lavanya Sudharshan, MS; and Margaret K. Pasquale, PhD
This study provides proof of concept that imminent risk of fracture can be assessed by evaluating recent fracture, age, sex, race, medically significant falls, and psychoactive medications.

Objectives: To develop and validate predictive models for imminent fracture risk in a Medicare population.

Study Design: This retrospective administrative claims (Humana Research Database) study assessed imminent risk in Humana’s Medicare Advantage and Prescription Drug plan members.

Methods: Individuals (aged 67-87 years on January 1, 2015 [index]) with 1 year or more of history were followed for 3 months to up to 2 years, with censoring at death/disenrollment. The cohort was split into training and validation samples (1:1). Cox regression models assessed demographics, fracture history, medically significant falls, osteoporosis-related factors, frailty markers, and selected medications and comorbidities for independent predictors (P <.001) of incident nontraumatic clinical fractures in 12 and 24 months. A 6-variable model of 12-month risk used a published method for the risk-scoring point system.

Results: Of 1,287,354 individuals (mean age, 74.3 years; 56% female; 84% white), 3.8% had at least 1 fragility fracture at 12-month follow-up; 6.6% experienced fracture at 24 months (women vs men: 12 months, 4.8% vs 2.5%; 24 months, 8.3% vs 4.4%; both P <.01). At 12 months, recent fracture conferred approximately 3-fold-higher fracture risk (vs no recent fracture). Older age, white race, female sex, osteoporosis-related screening/diagnosis/medication, antidepressant/antipsychotic/sedative hypnotic/muscle relaxant medications, history of falls, fracture history, and respiratory conditions also increased risk (all P <.0001). The simplified model (recent fracture, age, sex, race, falls, antidepressant/antipsychotic/sedative hypnotic/muscle relaxant medications) performed well (C statistic = 0.71).

Conclusions: Recent fracture, older age, female sex, white race, falls, and antidepressant/antipsychotic/sedative hypnotic/muscle relaxant medications predict imminent fracture risk in an older-adult Medicare Advantage population. Imminent fracture risk can be assessed using 6 easily quantified factors.

Am J Manag Care. 2020;26(3):e91-e97.
Takeaway Points
  • Guideline-recommended tools that estimate long-term (10-year) fracture risk are used for osteoporosis treatment decisions, but these tools do not quantify imminent (in the next 1-2 years) risk.
  • In our validated predictive models for imminent (1-year) fracture risk in the elderly population, age, race, sex, osteoporosis-related screening/diagnosis, medically significant falls, antidepressant/antipsychotic/sedative hypnotic/muscle relaxant medications, history of fracture, respiratory disorders, nervous system disorders, physical factors, and additional comorbidities/medications were significantly associated with greater imminent fracture risk.
  • A simplified model (recent fracture, age, sex, race, falls, and antidepressant/antipsychotic/sedative hypnotic/muscle relaxant medications) supports feasibility for hand-calculating imminent risk during routine visits.
Up to 25% of men and 50% of women will experience a fracture in their remaining lifetime after age 50 years.1 Osteoporosis-related fractures confer significant direct medical costs, quality-of-life decrements and functional disability, and indirect costs (lost productivity and caregiver burden).2-7 By 2025, fracture-related direct treatment costs are expected to reach $25.3 billion in the United States.2,6 The impact of fractures to individuals may be long-lasting and result in increased use of healthcare services, a greater likelihood of hospitalization and skilled nursing care, reduced economic circumstances, and increased mortality risk for up to 10 years post fracture.3,4,7,8

Various antiresorptive and bone-forming therapies have received FDA approval based on their ability to reduce the risk of fracture in men and women with osteoporosis.9 Fracture risk-assessment tools help clinicians estimate the risk of osteoporosis-related fracture in their patients, and these estimates inform treatment recommendations. The most commonly used tools, such as FRAX,10 focus exclusively on long-term fracture risk (ie, 10-year time horizon). The literature suggests that the imminent risk (ie, in next 1-2 years) of fracture also has important implications for treatment decisions.10-15 Imminent risk is responsive to changes in bone mineral density (BMD), fracture, and fall history, as well as factors that influence physical or cognitive functioning in ways that are not captured in existing tools.10,13-17 Furthermore, patients with osteoporosis may not perceive fracture risk accurately, and long-term risk assessments, in conjunction with patients’ potentially incomplete understanding of the relationship between osteoporosis and fracture risk, may not provide sufficient motivation for treatment initiation.18-20

Elevated imminent risk may require a different treatment approach from fracture risk that accumulates or extends over a longer time frame.10,14 The objective of this study was to develop and validate predictive models for imminent risk of fracture in a population of older adults enrolled in Humana’s Medicare Advantage and Prescription Drug (MAPD) plans. This paper describes the primary full model, which includes an extensive set of predictors for the outcome of any fracture within a 12-month follow-up, and a parsimonious model, which was developed to provide proof of concept for a risk-assessment tool that could easily be used for hand-calculating risk during a routine physician office visit.


Data Source and Population

This retrospective database study used a cohort design and multivariate analysis to identify predictors of imminent fracture risk in older adults enrolled in Humana MAPD plans. The Humana Research Database (Humana; Louisville, Kentucky), which contains administrative data for Humana’s fully insured commercial and Medicare individuals, was used. Data on MAPD enrollment, medical claims, and outpatient pharmacy claims were linked for each individual. The study period—January 1, 2014, through December 31, 2016—was split into a 1-year baseline period (January 1, 2014, through December 31, 2014) and a 2-year follow-up period (January 1, 2015, through December 31, 2016).

All study individuals were aged 67 to 87 years on the index date (January 1, 2015) and had continuous enrollment in an MAPD plan throughout the baseline period and for at least the first 3 months of the follow-up period. Follow-up was censored at the date of death or plan disenrollment for individuals lost to follow-up before the end of study. Individuals with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis of either nonmelanomatous cancer or Paget disease of the bone and individuals enrolled in administrative services–only health plans or in a Humana health plan which is contractually excluded from research studies were excluded.

The sample was split into a randomly generated training (development) sample and a validation sample, with a 1:1 ratio. The primary study outcome was defined as incident fragility fracture. These fractures were identified using a combination of ICD-9-CM and ICD-10-CM diagnosis codes. Clinical fragility (nontraumatic) fractures with an osteoporosis likelihood score of 8 or greater, as defined by Warriner et al,21 were identified during 12- and 24-month follow-up intervals. This published algorithm was developed to enhance the accuracy of identifying osteoporosis-related fractures in administrative claims data and was used in the current study to reduce the potential for misclassification of the primary study outcome. Fracture codes recorded during the follow-up period but within 60 days of a baseline fracture were considered as a continuation of care for the baseline fracture and, therefore, not considered in the analysis of fracture outcomes during follow-up.

Covariates considered as potential independent variables for the predictive models included patient demographics (age, sex, race, and geographic region), history of fracture, falls that result in medical encounters or that require treatment (ie, medically significant falls), BMD testing, comorbidities, medication use, and markers of frailty. Comorbidities were quantified by the Deyo-Charlson Comorbidity Index22 score and yes/no indicator variables for selected comorbidities, including those associated with an increased likelihood of fractures/medically significant falls. Osteoporosis treatments, as well as medications associated with an increased likelihood of fractures/medically significant falls (eg, antihypertensives, anticonvulsants, antidepressants, antipsychotics), were assessed. Markers of frailty included data on difficulty walking, use of durable medical equipment or ambulance/life support, paralysis, weakness, and podiatric care.

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