Diagnosing and managing osteoporosis in primary care
Osteoporosis (OP) is a disabling condition associated with significant morbidity and mortality. Management of OP requires a multidisciplinary approach, with choice of treatment based on patients’ fracture risk.
At a virtual symposium organized by the Osteoporosis Society of Hong Kong (OSHK), Dr Tai-Pang Ip, Specialist in Endocrinology, Diabetes and Metabolism in Hong Kong, and Dr Sze-Hung Wong, Specialist in Orthopaedics and Traumatology in Hong Kong, discussed the diagnosis and management of OP in primary care and the role of antiresorptive and bone-forming agents in treatment of OP in high-risk patients.
Diagnosis of OP in primary care
“OP is the most common metabolic bone disease, with a prevalence of 33.3 percent in postmenopausal women and 20 percent in men aged ≥50 years. The incidence of osteoporotic fractures is higher than that of myocardial infarction, stroke and breast cancer combined,” said Ip. [J Bone Miner Res 2007;22:465-75; Circulation 2016;133:e38-e360; CA Cancer J Clin 2016;66:7-30]
Diagnosis is based on a bone mineral density (BMD) T-score of ≤-2.5 at lumbar spine or proximal femur, measured by dual-energy X-ray absorptiometry (DXA). [J Bone Miner Res 1994;9:1137-1141] “Patients undergoing DXA scans should be correctly positioned for central DXA scan to be taken at the hip and spine,” said Ip. [J Clin Densitom 2016;19;127-140]
A basic laboratory work-up is advised, and subsequent specialist referral may be needed in patients with potential secondary causes of OP. [Hong Kong Med J 2013;19(Suppl 2):1-40]
“The Hong Kong population-specific Fracture Risk Assessment Tool [FRAX] can be used to assess patients’ 10-year probability of major osteoporotic fracture [MOF] or hip fracture, particularly in those with BMD in the osteopenic range, to decide on the need of medical treatment,” Ip added. [http://www.shef.ac.uk/FRAX]
Initiating and choosing a treatment for OP
According to the OSHK’s guideline, treatment of OP is indicated in postmenopausal women and men ≥50 years of age with prior hip or spine fracture, or a BMD T-score ≤-2.5 at the spine or proximal femur, or those with osteopenia and a FRAX 10-year MOF risk of ≥20 percent or a FRAX 10-year hip fracture risk of ≥3 percent. Recently, a local study suggested a lower treatment threshold of a FRAX 10-year MOF risk of ≥9.95 percent may be more appropriate. (Figure) [Hong Kong Med J 2013;19(Suppl 2):1-40; Osteoporos Int 2014;25:1017-1023]
“The best timing for initiation of anti-osteoporotic therapy is in the immediate post-fracture period, since the imminent fracture risk [ie, risk of second MOF in the next 12–24 months] is almost three-fold higher than the population risk,” said Ip. [Osteoporos Int 2017;28:775-780]
“Management of OP requires a multidisciplinary approach with emphasis on fall prevention through multifactorial assessment, along with calcium and vitamin D supplementation,” he continued. [JAMA 2017;318:1687-1699] “It is also important to review patients’ existing medications and consider replacing nonessential fracture-associated drugs with alternatives.”
“Treatment adherence is crucial in OP since poor adherence to therapy is known to have a negative impact on fracture risk,” he emphasized. [Bone 2006;38:922-928]
Choosing an antiresorptive agent
The choice of OP treatment should be based on patients’ fracture risk. Potent antiresorptive agents, such as denosumab, is indicated in high-risk patients (ie, ≥65 years of age with FRAX 10-year MOF probability ≥9.95 percent or hip fracture probability ≥3 percent, or prior fracture within 24 months, or BMD T-score ≤-2.5 at lumbar spine or proximal femur on DXA). [Hong Kong Med J 2013;19 (Suppl 2):1-40; Osteoporos Int 2014;25:1017-1023]
Denosumab, a fully human monoclonal antibody, acts by binding to the receptor activator of nuclear factor-ƙB ligand (RANKL), thereby inhibiting the activity of osteoclasts and decreasing the rate of remodelling. [Lancet 2019;393:364-376]
Notably, denosumab is not incorporated into bone, and its effects on BMD and bone turnover markers are reversed upon drug discontinuation. [Drugs Aging 2018;35:163-173; J Clin Endocrinol Metab 2011;96:972-980]
“Drug holiday is therefore inappropriate in patients on denosumab therapy, and its discontinuation should always be followed by bisphosphonate treatment to prevent rebound bone loss,” pointed out Ip. [Bone 2017;105:11-17]
FREEDOM extension study: Long-term efficacy and safety
In the open-label FREEDOM extension study, 1,343 postmenopausal women with a lumbar spine or total hip BMD T-score <-2.5 at either location but >-4.0 at both locations who had received 3 years of denosumab 60 mg subcutaneously were continued on denosumab (long-term group), while 1,283 patients who had received 3 years of placebo were switched to denosumab (cross-over group). In both groups, denosumab was given for up to 7 years. [Lancet Diabetes Endocrinol 2017;5:513-523]
Long-term denosumab demonstrated consistent benefit in lowering the risk and cumulative incidence of new vertebral and nonvertebral fractures vs virtual twin placebo (new vertebral fractures, 7.0 percent vs 11.5 percent; RR, 0.62; 95 percent CI, 0.47 to 0.80) (nonvertebral fractures, 9.3 percent vs 14.5 percent; RR, 0.54; 95 percent CI, 0.43 to 0.68). [Lancet Diabetes Endocrinol 2017;5:513-523]
Continuous relative increases in BMD from FREEDOM baseline were shown in the denosumab group vs the placebo and subsequent cross-over group for lumbar spine (21.7 percent vs 16.5 percent), total hip (9.2 percent vs 7.4 percent), femoral neck (9.0 percent vs 7.1 percent ) and one-third radius (2.7 percent vs 2.3 percent).
The yearly exposure-adjusted incidence of all adverse events (AEs) with denosumab decreased from 165.3 to 95.9 per 100 participant-years over the course of 10 years, with infections (23.0–35.1 percent), malignancies (1.6–2.7 percent) and eczema (0.7–1.4 percent) being the most common AEs.