New research was presented at the American Society for Bone and Mineral Research (ASBMR) 2022 annual meeting, held September 9-12 in Austin, TX. The features below highlight some of the studies emerging from the conference.

FRAX Remains a Valid Tool for Predicting Fracture Risk in RA

For patients with rheumatoid arthritis (RA), the Fracture Risk Assessment Tool (FRAX) demonstrated efficacy for predicting risk for osteoporotic fractures. Among patients with RA treated over the past two decades, the mean predicted 10- year risk for major osteoporotic fractures (MOF) was 13.2% according to FRAX with bone mineral density, which the researchers observed as a “good overall calibration.” Therefore, FRAX can continue to be used for the management of osteoporosis in patients with RA, the study authors wrote. About 20% of patients in the study had a previous fracture, the majority were White and female, and participants ranged in age from 62 to 65. MOF in a 10-year period was the primary endpoint. Glucocorticosteroid use was more frequent in the RA group (28% vs 4%). The RA group had more MOF cases, 15.6 per 1,000 person-years, versus 11.7 cases per 1,000 person-years in the non-RA group. The study team did note that low exposure to biologics may have impacted the trial’s outcome, as only about 10% of patients with RA were using biologics and 81% were taking other disease-modifying agents. They originally thought that biologics would result in lower risk for MOF.

Daily Vitamin D Supplementation Does Not Prevent Fractures

Daily vitamin D supplementation does not prevent fractures in low-risk adults older than 50, according to an adjuvant study from the VITAL trial. Meryl LeBoff, MD, and colleagues reported that individuals taking 2,000 IUs of vitamin D daily over a median 5.3 years of follow-up did not experience a notable effect on two site-specific fracture types: hip fractures (HR, 1.01; 95% CI, 0.70-1.47) and nonvertebral fractures (HR, 0.97; 95% CI, 0.87- 1.07). The study consisted of healthy midlife and older adults (N=25,871; 50.6% women; 20.2% Black), with no low bone mass, osteoporosis, and vitamin D deficiencies at baseline. For most participants, Dr. LeBoff and colleagues noted, calcium was not co-administered with daily vitamin D supplementation. However, no differences were reported in the 20% of participants who did take up to 1,200 mg of calcium daily. Excluded from the investigation were fractures of the fingers, skull, or toes, as well as pathologic and periprosthetic fractures. These findings mirror previous research on vitamin D supplementation, presented at the 2021 ASBMR annual meeting, which found no effect on total fracture risk (HR, 0.98; 95% CI, 0.89-1.08). In addition, the study team observed no considerable differences between groups for major osteoporotic fractures of the hip, humerus, wrist, or clinical spine (HR, 0.99; 95% CI, 0.83-1.17), wrist fractures (HR, 0.89; 95% CI, 0.69-1.15), and pelvic fractures (HR, 1.08; 95% CI, 0.64-1.80). Even when accounting for baseline characteristics such as age, BMI, ethnicity, race, sex, and serum 25-hydroxyvitamin D levels, the findings remained consistent. The study authors noted that ongoing research about vitamin D levels or genetic variation in vitamin D levels will reveal information about the link between musculoskeletal health and supplemental vitamin D.

Global Hip Fracture Declined, But May Double by 2050

The rate of hip fractures droppe by as much as 2.8% a year in 11 regions around the world, but the aging population means the number of fractures is predicted to double by 2050, according to Douglas Kiel, MD, MPH, and colleagues. Dr. Kiel pointed out that there will be a 4.5-fold increase in world population of people aged 85 and older and that there was a “large post-fracture treatment gap in fracture prevention across all countries through the study period” from 2005 to 2018. The investigation was based on an evaluation of 20 healthcare databases from 19 regions and countries. Apprehensions about adverse events linked with antiresorptive therapies was one reason for this treatment gap, the study authors noted. Hip fracture burden was more common in men than in women, with men having a higher mortality rate. Within a year of sustaining a hip fracture, all-cause mortality among men extended from 19.2% to 35.8% versus 12.1% to 25.4% among women. Dr. Kiel and colleagues observed that in the United Kingdom, 50.3% of patients reported that they were undergoing preventive treatment within 1 year of a hip fracture. In contrast, just 35% of patients in the United States reported the same; the post-fracture treatment rate in some other countries was as low as 11%. In individuals older than 85, the study authors observed that the incidence of hip fracture was more than two-fold greater than that of people aged 80 to 84. Dr. Kiel and colleagues agreed that researchers need to determine why a treatment gap exists and why only 50% of patients with fracture history are being treated to prevent further fracture and osteoporosis.

Denosumab Carries No Increased Risk for CV Disease or Stroke

Patients with osteoporosis being treated with denosumab experienced no increased risk for cardiovascular disease or stroke when compared with zoledronic acid, according to Tzu-Chieh Lin, PhD, BPharm, MClinPharm, and colleagues. Compared with zoledronic acid, denosumab had no significant impact on myocardial infarction risk at 36 months in either the Optum medical database (aRR, 0.97; 95% CI, 0.63-1.32) or the MarketScan database (aRR, 1.22; 95% CI, 0.77-1.66), the study authors noted, adding that findings were similar for the rate for stroke (Optum database: aRR, 0.87 [95% CI, 0.56- 1.17]; MarketScan database: aRR, 1.00 [95% CI, 0.61-1.40]). Dr. Lin and colleagues conducted a retrospective study using the two major US claims databases, identifying individuals aged 55 and older being treated with either zoledronic acid or denosumab. In the Optum database, 73,127 patients were followed for a mean of 350 days, while in the Marketscan database, 96,611 patients had a mean follow-up of 385 days. Women comprised nearly 90% of study participants. Researchers observed about 715 stroke events and 500 myocardial infarction events in both databases. Dr. Lin said the study was conducted due to inconsistent evidence published regarding cardiovascular and cerebrovascular risks and benefits for anti-osteoporosis medications. Key strengths of the study, he added, were the large database sizes and that its duration allowed researchers to fully observe outcomes.

Romosozumab Plus Denosumab Improves BMD, Reduced Fracture

Compared with 2 years of denosumab, improved bone mineral density (BMD) and lower fracture incidence were observed in women with osteoporosis after initiating 1 year of romosozumab followed by a year of denosumab, according to results from a clinical trial. Felicia Cosman, MD, and colleagues conducted the FRActure study in postmenopausal woMen with ostEoporosis (FRAME) among women aged 55 and older. Participants were randomized 1:1 to placebo or romosozumab 210 mg subcutaneous injection every month for 12 months. For every 6 months for 12 months afterward, they were also administered a subcutaneous injection of denosumab 60 mg. In the FRAME Extension study, both groups then received denosumab for 12 months. Dr. Cosman and colleagues compared years 1 and 2 of the investigative arm with years 2 and 3 of the comparator arm. Using the inverse probability of treatment weighting to estimate the treatment effect, the study team was able to perform sensitivity analyses. They reported that first-line treatment with romosozumab was linked with a 16.8% increase in BMD in the lumbar spine, compared with a 7.4% increase with 2 years of denosumab. They also observed an increase of 7.6% versus 3.4% in the femoral neck and an increase of 8.4% versus 3.9% in the total hip. Dr. Cosman noted that a decrease in new vertebral fractures was linked with the romosozumab-first approach, compared with 2 years of denosumab (0.6% vs 1.3%).