Medical Care Use Among Patients with Monogenic Osteoporosis Due to Rare Variants in LRP5, PLS3, or WNT1

Abstract

Pathogenic variants in the LRP5, PLS3, or WNT1 genes can significantly affect bone mineral density, causing monogenic osteoporosis. Much remains to be discovered about the phenotype and medical care needs of these patients. The purpose of this study was to examine the use of medical care among Dutch individuals identified between 2014 and 2021 with a pathogenic or suspicious rare variant in LRP5, PLS3, or WNT1. In addition, the aim was to compare their medical care utilization to both the overall Dutch population and the Dutch Osteogenesis Imperfecta (OI) population. The Amsterdam UMC Genome Database was used to match 92 patients with the Statistics Netherlands (CBS) cohort. Patients were categorized based on their harbored variants: LRP5, PLS3, or WNT1. Hospital admissions, outpatient visits, medication data, and diagnosis treatment combinations (DTCs) were compared between the variant groups and, when possible, to the total population and OI population. Compared to the total population, patients with an LRP5, PLS3, or WNT1 variant had 1.63 times more hospital admissions, 2.0 times more opened DTCs, and a greater proportion using medication. Compared to OI patients, they had 0.62 times fewer admissions. Dutch patients with an LRP5, PLS3, or WNT1 variant appear to require on average more medical care than the total population. As expected, they made higher use of care at the surgical and orthopedic departments. Additionally, they used more care at the audiological centers and the otorhinolaryngology (ENT) department, suggesting a higher risk of hearing-related problems.

Keywords: Early-onset osteoporosis; LRP5; Monogenic osteoporosis; Osteogenesis imperfecta; PLS3; WNT1.

Fig. 1

Characteristics of patients identified between 2014 and 2021 with LRP5, PLS3 or WNT1 variants in the Amsterdam UMC Genome Database

Fig. 2

The proportion of people using medication according to ATC main groups; comparing patients with a pathogenic or a rare suspicious variant in LRP5, PLS3, or WNT1 to the total Dutch population. Due to patient privacy, absolute numbers for certain categories cannot be shown; this is indicated by capped lines. For patients 0–24 years old, values ≤14% are not shown; for patients 45–64 years old, values ≥88% are not shown; for patients 65 years and older, values ≥79% are not shown. Y, years. For more information on ATC main groups the ATC/DDD index of the WHO Collaborating Centre for Drug Statistics Methodology can be consulted [27]. ATC, Anatomical Therapeutic Chemical; DDD, defined daily dose; WHO, World Health Organization.