FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.
Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal.


INTRODUCTION
We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation.


METHOD
One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs.


RESULTS
The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis.


CONCLUSION
The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.
['Chandran|M|M|', 'McCloskey|E V|EV|', 'Thu|W P P|WPP|', 'Logan|S|S|', 'Hao|Y|Y|', 'Tay|D|D|', 'Ang|W C|WC|', 'Aung|T K K|TKK|', 'Choo|K S|KS|', 'Ali|A|A|', 'Yan|S X|SX|', 'Huang|X F|XF|', 'Liu|X M|XM|', 'Yong|E L|EL|', 'Lekamwasam|S|S|']
D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D044466:Asians D015519:Bone Density D050071:Bone Density Conservation Agents D005260:Female D006620:Hip Fractures D006801:Humans D008875:Middle Aged D015663:Osteoporosis, Postmenopausal D058866:Osteoporotic Fractures D017698:Postmenopause D018570:Risk Assessment D012307:Risk Factors D012680:Sensitivity and Specificity D012720:Severity of Illness Index D012846:Singapore
FRAX Intervention threshold Osteoporosis Singapore Fragility fracture Guidelines Treatment threshold