Circulating fractures-related microRNAs distinguish primary hyperparathyroidism-related from estrogen withdrawal-related osteoporosis in postmenopausal osteoporotic women: A pilot study.

Primary hyperparathyroidism (PHPT) represents a common cause of secondary osteoporosis in postmenopausal women, where the negative effect of estrogen withdrawal and that of hyperparathyroidism on bone mineralization coexist. Circulating microRNAs (miRNAs) expression profile has been correlated to both osteoporosis and fragility fractures. The study aimed to profile a set of miRNAs associated with osteoporotic fractures, namely 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 20 postmenopausal PHPT women. PHPT miRNAs profiles were compared with those detected in 10 age-matched postmenopausal non-PHPT osteoporotic women (OP). All the 10 miRNAs were detected in the plasma samples of both PHPT and OP women. The miRNA profiles clearly distinguished PHPT from OP samples, and identified within the PHPT group, two clusters differing for the PHPT severity, in term of ionized calcium and bone mineralization. In particular, miR-93-5p was significantly downregulated in PHPT samples, while miR-24-3p negatively correlated with the T-score at lumbar, femur neck and total hip sites. PHPT women who experienced osteoporotic fractures had plasma miR-24-3p levels higher than those detected in unfractured PHPT women. In conclusion, PHPT may modulate circulating fractures-related miRNAs, in particular, miR-93-5p, which may distinguish estrogen-related from PHPT-related osteoporosis.

Circulating IL-17A Levels in Postmenopausal Women with Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. AIM: To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n = 20). RESULTS: Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P = 0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r = -0.294, P = 0.047) and urine calcium excretions (r = -0.300, P = 0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r = 0.364, P = 0.021) and total hip (r = 0.353, P = 0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. CONCLUSIONS: In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.

Standard and water rehabilitation: An analysis of over 14 years' experience in patients with haemophilia or other clotting factor disorders after orthopaedic surgery.

INTRODUCTION: In people with haemophilia (PWH) with severe arthropathy, total joint replacement (TJR) can be undertaken if conservative management fails. Post-operative rehabilitation treatment is an important part of the comprehensive management of patients undergoing TJR. AIM: To compare post-operative standard rehabilitation (SR) and SR plus water rehabilitation (WR) in PWH undergoing TJR. METHODS: PWH who were admitted to our centre between June 2003 and December 2016 for rehabilitation after TJR were included in the study. Rehabilitation included SR (ie, manual and mechanical mobilization, scar tissue massage, light muscle strengthening exercises and walking training with and without crutches) with or without WR. WR exercises with floats of different size and volume were performed when possible. Range of motion (ROM), muscle strength, pain level, perceived health status and length of hospital stay were analysed retrospectively. RESULTS: A total of 184 patients (233 rehabilitation programmes were enrolled in the study, corresponding to 160 after total knee replacement [TKR], 37 after total ankle replacement [TAR] and 36 after total hip replacement [THR]). Fifty-eight (25%) patients were treated with WR in addition to SR (32 for TKR, 19 for TAR and 7 for THR) with an average of 5.7 hours of WR. Muscle strength, pain and perceived health status improved significantly after rehabilitation. CONCLUSION: This non-randomized study seems to indicate that WR plus SR improves muscle strength, pain and perceived health status more than SR alone in PWH undergoing TJR. It would be necessary, however, to carry out randomized comparative studies to confirm these provisional conclusions.

Symptomatic Hypercalcemia in Patients with Primary Hyperparathyroidism Is Associated with Severity of Disease, Polypharmacy, and Comorbidity.

Current primary hyperparathyroidism (PHPT) clinical presentation is asymptomatic in more than 90% of patients, while symptoms concern osteoporosis and rarely kidney stones. Here, we retrospectively investigated the prevalence of PHPT patients presenting with hypercalcemic-related symptoms (HS-PHPT) as cognitive impairment, changes in sensorium, proximal muscle weakness, nausea and vomiting, constipation, and severe dehydration, in a single center equipped with an emergency department and described their clinical features and outcome in comparison with a series of asymptomatic PHPT out-patients (A-PHPT). From 2006 to 2016, 112 PHPT patients were consecutively diagnosed: 16% (n = 18, 3M/15F) presented with hypercalcemic-related symptoms. Gastrointestinal symptoms occurred in 66% of HS-PHPT patients and cognitive impairment in 44%; one woman experienced hypertensive heart failure. Two-thirds of HS-PHPT patients were hospitalized due to the severity of symptoms. Comparing the clinical features of HS-PHPT patients with A-PHPT patients, no gender differences were detected in the two groups, while HS-PHPT patients were older at diagnosis (71 (61-81) vs. 64 (56-74) years, P=0.04; median (IQR)). HS-PHPT patients presented higher albumin-corrected calcium levels (12.3 (11.3-13.7) vs. 10.6 (10.3-11.3) mg/dl, P < 0.001); 4 HS-PHPT presented corrected calcium levels >14 mg/dl. Serum PTH levels and total alkaline phosphatase activity were higher in HS-PHPT. Reduced kidney function (eGFR < 45 ml/min) was prevalent in HS-PHPT patients (42% vs. 5%, P=0.05). No differences in kidney stones and osteoporosis were detected, as well as in the rates of cardiovascular comorbidities and main cardiovascular risk factors. HS-PHPT patients had an age-adjusted Charlson Comorbidity Index higher than that of the A-PHPT patients and were on chronic therapy with a greater number of medications than A-PHPT patients. In conclusion, hypercalcemic-related symptoms occurred in 16% of PHPT patients. Risk factors were severity of the parathyroid tumor function, multimorbidity, and polypharmacy.