The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects.

BACKGROUND: While the inverse relationship between serum ionized calcium (Ca2+) and PTH is well-established, the relationship between 25(OH)D and PTH showed conflicting results. The study aimed to evaluate the relative contributions of age, sex, serum Ca2+, ionized magnesium (Mg2+), 25(OH)D and 1,25(OH)2D in regulating PTH secretion in healthy subjects. METHODS: This is a secondary analysis of an observational study performed from March 2014 to July 2015 carried out in 2259 blood donors (1652 men and 607 women, age range 18-68 years). Subjects with parathyroid disorders and taking drugs that affect mineral metabolism were excluded. RESULTS: Significant correlations [between Ca2+ and PTH (r = -0.223, p < 0.001), 25(OH)D and PTH (r = -0.178, p < 0.001) and between PTH and age (r = 0.322, p < 0.001)] were found. As a preliminary step to multivariate analysis, a regression tree analysis was performed using PTH as response variable and age, Ca2+, Mg2+, 25(OH)D, 1,25(OH)2D and sex as explanatory variables to determine the effect of each covariate on the response variable. For subjects <38 years, 25(OH)D was the most important parameter in regulating PTH. For subjects ≥38 both 25(OH)D and Ca2+ levels regulated PTH secretion. Subjects with 25(OH)D < 13 ng/mL had average higher PTH; in this group only, subjects with Ca2+ ≥ 1.30 mmol/L had average lower PTH compared to subjects with Ca2+ < 1.30. The multivariate analysis showed that all variables had a significant effect (p < 0.001) on PTH. Anova Type III errors c indicated that 25(OH)D accounted for 32.1% of the total variance in PTH, Ca2+ accounted for 18% of the total variance, BMI for 14.3%, and 1,25(OH)2D for 11.1%. The remaining percentage was attributable to age and sex. This was confirmed by the regression tree approach, where 25(OH)D and Ca2+ accounted for the largest variation in the average levels of PTH. DISCUSSION: Under stable conditions 25(OH)D plays a significant role in regulating PTH secretion. Under conditions of relative vitamin D sufficiency, Ca2+ also plays an important role.

Acute effect of zoledronic acid on the risk of cardiac dysrhythmias.

There have been recent concerns regarding the risk of serious adverse events, such as cardiac dysrhythmia and atrial fibrillation (AF), associated with bisphosphonate use in osteoporosis. This open-label, non-randomized, crossover pilot study evaluated short-term effects of zoledronic acid and placebo on the occurrence of cardiac dysrhythmias and prodysrhythmic profile in postmenopausal women with osteoporosis and low risk of cardiac dysrhythmias. Fifteen postmenopausal women (mean age 70.7 ± 6.9 years) with osteoporosis received placebo infusion on day 1 and zoledronic acid 5 mg on day 7. Standard 12-lead resting EKG measured QT parameters at baseline and up to 24 h after infusion. Continuous 24-h EKG assessed dysrhythmic events and heart rate variability (HRV) for 24 h after infusion. There were no statistically significant differences in resting EKG parameters between placebo and zoledronic acid: QTc (404.28 ± 9.28 and 410.63 ± 18.43 ms), no significant differences in mean serum electrolytes at baseline and after infusion, and no significant association between QT/QTc parameters and serum electrolytes before and after each infusion (QTc: 401.83 ± 17.73 for zoledronic acid and 404.65 ± 16.79 for placebo). There was no significant difference in HRV parameters between placebo and zoledronic acid, and no dysrhythmias were recorded at rest or with 24 h EKG monitoring. Zoledronic acid does not produce dysrhythmia or prodysrhythmic effects in the short term. Among possible mechanisms proposed for cardiac dysrhythmias with zoledronic acid, no serum electrolyte or autonomous nervous system balance perturbations have been reported.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test.

OBJECTIVE: To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). METHODS: Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. RESULTS: Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. CONCLUSIONS: PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Muscle strength and bone in healthy women: effect of age and gonadal status.

OBJECTIVE: The aim of this work was to examine the effects of age and menopause on muscle strength and on the muscle-bone interaction. DESIGN: One hundred ninety-four healthy women (mean age 49.8 ± 12.6 SD years) were assessed. Maximal Voluntary Contraction (MVC, Newton, N) by Hand Grip Dynamometer, bone mineral density at one third of the radius (R-BMD) by dual-energy X-ray absorptiometry (DXA) and phalangeal ultrasound by the DBM Sonic 1200 device were evaluated at the upper dominant limb. Ultrasonometric parameters considered were Amplitude-Dependent Speed of Sound (ADSoS) and Ultrasound Bone Profile Index (UBPI). RESULTS: MVC significantly decreased with age (r²=-0.12, p<0.005). For each level of age, fertile women had a greater MVC compared to postmenopausal women (r²=0.015, p<0.005).In the whole sample, a statistically significant correlation between MVC and R-BMD (r=0.354, p<0.001) and between MVC and ADSoS (r=0.294) and UBPI (r=0.311)(p<0.001 for both) were observed. CONCLUSIONS: We conclude that age and menopausal status significantly contributed to the reduction of muscle strength. The decline of muscular strength significantly correlated with quantitative and qualitative bone features.