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Diagnosing and managing osteoporosis in primary care

Dr. Tai-Pang Ip
Specialist in Endocrinology, Diabetes and Metabolism
Hong Kong
Dr. Sze-Hung Wong
Specialist in Orthopaedics and Traumatology
Hong Kong
04 Sep 2020

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]

AMG-140md01

“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.

AMG-140md02


 

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Most Read Articles
Yesterday
Vitamin D deficiency may be a contributing factor to the mortality rate among patients with the novel coronavirus disease (COVID-19), reports a new study.
17 Nov 2020
Invasive fungal infections, particularly those caused by Candida species, are common in hospitalized, immunocompromised, or critically ill patients and are associated with considerable morbidity and mortality.
Roshini Claire Anthony, Yesterday

Initiation or switch to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide (TAF) led to low HIV-1 RNA viral load in people living with HIV (PLHIV), according to the BICSTaR study presented at HIV Glasgow 2020.

Christina Lau, 3 days ago

A synbiotic formula developed by researchers at the Chinese University of Hong Kong (CUHK) is shown to hasten recovery and increase the production of neutralizing antibodies in hospitalized patients with coronavirus disease 2019 (COVID-19).