4 New Things About Osteoporosis

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The latest research findings reveal new aspects of diagnosis, treatment, and prevention.

About 54 million Americans have osteoporosis or are at high risk because of low bone mass. Roughly 1 in 2 women and up to 1 in 4 men age 50 years and older will break a bone because they have osteoporosis.[[{"type":"media","view_mode":"media_crop","fid":"38069","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3241288862851","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8035","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 195px; width: 220px; border-width: 0px; border-style: solid; margin: 5px; float: right;","title":" ","typeof":"foaf:Image"}}]]

Each year, osteoporosis is responsible for 2 million broken bones and $19 billion in related costs. Those numbers are predicted to climb to about 3 million fractures and $25.3 billion in costs by 2025.

Several recent studies reported on new aspects of osteoporosis diagnosis, treatment, and prevention. Read on for brief summaries of the latest research findings.

 

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Bone Mineral Density Has Genetic Link

Researchers conducted a genome-wide association study in 142,487 patients to identify loci associated with bone mineral density (BMD) as estimated by quantitative ultrasound of the heel.

To investigate the underlying mechanisms, they undertook bioinformatic, functional genomic annotation and human osteoblast expression studies; gene-function prediction; skeletal phenotyping of knockout mice; and analysis of gene expression in mouse osteoblasts, osteocytes, and osteoclasts.

Identified were 307 conditionally independent single-nucleotide polymorphisms that attained genome-wide significance at 203 loci, explaining about 12% of the phenotypic variance.

Of these, 153 were previously unreported loci and several were rare variants with large effect sizes.

The gene GPC6 was implicated as a novel determinant of BMD and a potential candidate for a drug target.

Also identified were abnormal skeletal phenotypes in knockout mice associated with a further 100 prioritized genes.

The results could be used to develop screening programs to identify patients who would benefit most from preventive measures.

 

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Targeting Senescence Suggests a Novel Treatment Strategy

Researchers investigated a role for senescent cells in age-related bone loss, using genetic or pharmacological means to eliminate senescent cells. They also inhibited production of the proinflammatory secretome of senescent cells using a Janus kinase inhibitor.

In aged mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAK inhibitor for 2 to 4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice.

The beneficial effects of targeting senescent cells were the result of lower bone resorption with maintained (trabecular) or higher (cortical) bone formation compared with vehicle-treated mice.

Senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis.

The data established a causal role for senescent cells in bone loss with aging.

Targeting the cells was shown to have both antiresorptive and anabolic effects on bone.

Targeting this mechanism to prevent age-related bone loss suggests a novel treatment strategy for osteoporosis and for multiple age-related comorbidities.

 

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Self-perception of Fracture Risk Enhances Assessment

In an international cohort study that involved 723 physician practices across 10 countries, researchers assessed how well self-perception of fracture risk and fracture risk as estimated by FRAX relates to fracture incidence and uptake and persistence of anti-osteoporosis medication (AOM) among women aged 55 years and older.

Of the women with at least 1 year of follow-up data, 5.4% sustained an incident major osteoporotic fracture over 5 years of follow-up.

Within each self-perceived fracture risk (SPR) category, risk of fracture increased as the FRAX categorization of risk increased.

Only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women who had a higher SPR.

AOM use tended to increase in the years after a reported fracture, but women with a lower SPR who had a fracture still reported lower AOM rates than women who had a higher SPR, regardless of whether they had a fracture.

The authors concluded that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake.

They suggested that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment.

 

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Vitamin D Deficiency Lacking in Targeted Strategies

Researchers in Ireland investigated the prevalence and determinants of vitamin D deficiency in a representative sample of the older Irish population (persons aged 50 to 98 years).

They measured the concentration of 25-hydroxyvitamin D (25(OH)D) in 5356 community-dwelling older Irish adults from The Irish Longitudinal Study on Ageing (TILDA) and assessed detailed demographic, geographic, lifestyle, and socioeconomic factors by questionnaire.

The prevalence of deficiency (25(OH)D < 30nmol/L) was 13.1%.

Deficiency status was more prevalent in non–supplement users, in winter, in smokers, in obese adults, in the physically inactive, in those living alone, and in the oldest old (> 80 years).

The main predictors of 25(OH)D concentration were supplement use, smoking, summer season, and obesity.

The authors concluded that vitamin D deficiency is common in older Irish adults and targeted strategies are needed within sections of the older population to improve vitamin D status.

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