“Primary hyperparathyroidism (PHPT)-related osteoporosis is one of the most frequent causes of secondary osteoporosis, and it frequently occurs in postmenopausal women, with a prevalence of up to 1%,” explains Sabrina Corbetta, MD, PhD. “Primary hyperparathyroidism-related osteoporosis improves after successful parathyroid surgery to remove parathyroid adenoma and normalize circulating parathyroid hormone (PTH) and calcium levels, though it can improve in response to antiresorptive therapies. Therefore, distinguishing between estrogen withdrawal-related and primary hyperparathyroidism-related osteoporosis is relevant for the management and treatment of postmenopausal women who are at increased risk for fragility fractures. Moreover, estrogen withdrawal-related and primary hyperparathyroidism-related osteoporosis often coexist in the same patient.”

With circulating microRNAs (miRNAs) expression profile having been correlated with both osteoporosis and fragility fractures in prior research, Dr. Corbetta, Giovanni Lombardi, PhD, and colleagues sought to profile a set of miRNAs associated with osteoporotic fractures— miR-21-5p, miR-23a-5p, miR-24-2-5p, miR-24-3p, miR-93-5p, miR-100-5p, miR-122-5p, miR-124-3p, miR-125b-5p, and miR-148-3p—in the plasma of postmenopausal women with PHPT and compare them with those detected in age-matched postmenopausal with osteoporosis but without PHPT.

While each of the 10 miRNAs was detected in plasma samples of women with PHPT or osteoporosis, the profiles definitively distinguished PHPT from OP samples. Within the PHPT group, two clusters differed by PHPT severity, in terms of ionized calcium and bone mineralization. “In particular, circulating miR-93-5p levels were significantly reduced in women with PHPT and distinguished the two osteoporotic conditions with high sensitivity and specificity,” says Dr. Lombardi. On the other hand, miR-24-3p was negatively correlated with T-scores at the lumbar, femur neck, and total hip sites, with women who had PHPT and osteoporotic fractures experiencing plasma miR-24-3p levels that were higher in those with PHPT but no fractures.

“Our results need to be validated in a wide osteoporotic population, including women with primary hyperparathyroidism presenting with different clinical and biochemical features,” notes Dr. Corbetta. Detection of circulating miR-93-5p may provide a useful diagnostic tool to distinguish PHPT-related osteoporosis from estrogen withdrawal-related osteoporosis. In the meantime, physicians should consider the occurrence of PHPT in postmenopausal osteoporotic women, and diagnose and treat this condition according to current guidelines.”

Lombardi, G.; Ziemann, E.; Banfi, G.; Corbetta, S. Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism. Int. J. Mol. Sci. 2020, 21, 5388.