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Aims: The pilot study was designed to evaluate the early effect of intravenous (i.v.) zoledronic acid (ZA) on renal function., Methods: Five mg i.v. ZA was administered to 23 patients with osteoporosis (17 women and 6 men, mean age 73 ± 7 SD years). Urinary NGAL, KIM-1, and MCP-1, plasma (p) MCP-1 and serum (s) IL-18, serum calcium (sCa), Creatinine clearance (CrCl), parathyroid hormone (PTH), plasma C-terminal FGF23 (pFGF23), serum (s) Klotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO 4 /GFR) were assessed at baseline, 24 h and Day 30 after administration., Results: There was a significant decrease in sCa and CaEx at 24 h (-4.1 ± 2.8%, P < 0.01 and -28 ± 59%, P < 0.05, respectively) and Day 30 (-3.9 ± 4%, P < 0.001 and -26 ± 43%, P < 0.01) and a significant increase in PTH (79.8 ± 95.8%) at Day 30 (P < 0.001) compared to baseline. TmPO 4 /GFR decreased significantly at 24 h and Day 30 (-8.6 ± 15.9%, P < 0.05 and -11.3 ± 13.5%, P < 0.001) compared to baseline. We observed no difference in the concentration of pFGF23, sKlotho and urinary AKI biomarkers at any time points. Mean levels of sIL-18 and pMCP-1 increased significantly at 24 h (44 ± 88%; P < 0.01 and 198 ± 237%; P < 0.001) and returned to baseline at Day 30., Conclusions: Our pilot study suggests that there is no direct acute effect of ZA on kidney function. The increase in plasma MCP-1 and serum IL-18 concentration could be associated with the stimulation of immunity mechanisms occurring soon after the administration of the drug. Secondary hyperparathyroidism develops shortly after the infusion of ZA and is maintained even after 1 month., (© 2017 The British Pharmacological Society.)

Our study investigated the patterns of treatment and adherence to prescribed therapies in 2,191 ambulatory patients with previous hip osteoporotic fractures at 207 participating orthopedic centers throughout Italy. All patients who came to the attention of the involved orthopedic surgeons were administered a questionnaire investigating: age, sex, height, weight, date of admission and length of stay in the hospital, other previous clinical fractures, bone density or biochemical testing concerning mineral metabolism, treatment with bone-active drugs in the six months before the fracture, treatment after discharge from the hospital, continuous use of prescribed drugs, pain at the site of hip surgery, and comorbidity. A multivariate logistic regression model was applied, considering a subset of the variables in the questionnaire, in order to determine the factors that significantly influenced discontinuation of treatment after hip fracture. Among the patients, 88.1% were female and 86.2% of the subjects were older than 65. The mean length of hospital stay for hip fracture was 19.0+/-25.3 days. At the time of interview, the mean time elapsed since hospitalization was 542.9+/-1,197.3 days. A previous clinical fracture was referred by 20.2% of patients. Before hip fracture occurrence, 52.8% of patients had never received any kind of treatment, and this figure reached 80% if we also included those who had taken only calcium and/or vitamin D. Corresponding proportions after fracture were 22% and 31.3%, respectively. Finally, 52% of patients had stopped treatment given for osteoporosis after a mean period of 1.4 years. According to the results of the logistic regression, increasing age, pain [odds ratio (OR): 1.36; 95% confidence interval (CI): 1.21-1.65] and no use of diagnostic tests (OR: 2.46; CI: 1.79-3.37) showed a positive effect on the probability of quitting the medication. On the other hand, being female reduces by half (OR: 0.49; CI: 0.37-0.45) the probability of quitting medication. Our data showed a low rate of primary prevention, a still insufficient post-fracture therapy, along with a high rate of early discontinuation of osteoporosis medication in patients with previous hip fracture.

Context: Hypoparathyroidism is a rare endocrine disorder whose skeletal features include suppression of bone turnover and greater volume and width of the trabecular compartment. Few and inconsistent data are available on the prevalence of vertebral fractures (VF).Objective: To evaluate the prevalence of VF assessed by vertebral fracture assessment (VFA) in postmenopausal women with chronic postsurgical hypoparathyroidism.Design: Cross-sectional study.Setting: Ambulatory referral center.Patients or Other Participants: Fifty postmenopausal women (mean age 65.4 ± 9 years) with chronic postsurgical hypoparathyroidism and 40 age-matched healthy postmenopausal women (mean age 64.2 ± 8.6).Main Outcome Measures: Lumbar spine, femoral neck, and total hip bone mineral density were measured by dual X-ray absorptiometry (Hologic Inc., USA) in all subjects. Site-matched spine trabecular bone score was calculated by TBS iNsight (Medimaps, Switzerland). Assessment of VF was made by VFA (iDXA, Lunar GE, USA) using the semiquantitative method and the algorithm-based qualitative assessment.Results: All-site BMD values were higher in the hypoparathyroid vs the control group. By VFA, we observed a 16% prevalence of VF in hypoparathyroid women vs 7.5% in control subjects. Among those with hypoparathyroidism who fractured, 5 (62.5%) had grade 1 wedge, 2 (25%) had grade 2 wedge, and 1 (12.5%) had grade 2 wedge and grade 2 biconcave VF. In the hypoparathyroid group, 57% with VFs and 32% without VFs had symptoms of hypoparathyroidism.Conclusion: We demonstrate for the first time that in postmenopausal women with chronic postsurgical hypoparathyroidism, VFs are demonstrable by VFA despite normal BMD. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) (1‐84) improves lumbar spine (LS) areal bone mineral density (aBMD) and trabecular bone score (TBS) in hypoparathyroidism over a 2‐year treatment period. Studies in osteoporosis have shown that with PTH(1‐34) there is a significant increase in LS aBMD and TBS. In this article, we provide new data comparing the effects of the same form of PTH, namely recombinant human PTH, rhPTH(1‐84), on aBMD and TBS in hypoparathyroid and osteoporotic patients over an 18‐month treatment period. We studied 19 premenopausal (mean age 45.8 ± 11.8 years) and 16 postmenopausal (71 ± 8.4 years) hypoparathyroid women and 38 women with postmenopausal osteoporosis (71 ± 8.3 years). DXA (hologic) at LS, femoral neck, total hip, and distal one‐third radius was assessed. Site‐matched LS TBS data were extracted from deidentified spine DXA scans using the TBS iNsight software (version 2.1; Medimaps, Geneva, Switzerland). We observed a significant increase in LS aBMD in premenopausal and postmenopausal hypoparathyroid (3 ± 1.1%, p < 0.02 and 3.1 ± 1.4%, p < 0.05, respectively) and osteoporosis (6.2 ± 1.1%, p < 0.0001) patients after 18 months. There was a significant increase (3 ± 1.5%, p = 0.05) in TBS in premenopausal hypoparathyroid patients. A change in TBS was not observed in either postmenopausal group. One‐third radius aBMD significantly declined in postmenopausal hypoparathyroid (‐3.6 ± 1.1%, p < 0.01) and osteoporosis (‐8 ± 1.4%, p < 0.0001) patients. Overall, there was a significantly greater increase in TBS in premenopausal hypoparathyroid than in osteoporosis patients (p < 0.0001) after adjusting for baseline values, age, BMI, and average daily dose of rhPTH(1‐84). Comparing only postmenopausal women, the LS aBMD increase was greater in osteoporotic than hypoparathyroid subjects (p < 0.01). Our results demonstrate that rhPTH(1‐84) administered for 18 months increases trabecular aBMD in hypoparathyroidism and postmenopausal osteoporosis with greater gains observed in the subjects with osteoporosis. The data suggest different effects of PTH on bone depending on the baseline skeletal structure, skeletal dynamics, compartments, and menopausal status. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the role of trabecular bone score (TBS) as determinant in the risk for vertebral fracture (VF) and define specific TBS threshold/s in women with postmenopausal osteoporosis. We studied 107 women with postmenopausal osteoporosis characterized by L1-L4 T-score ≤ −3.0 with (group 1) and without (group 2) VF, or L1-L4 T-score ≤ −1.0 and ≥ −2.4 and multiple vertebral fractures (VF) (group 3). We assessed 30 postmenopausal women with L1-L4 T-score ≤ −1.0 and ≥ −2.4 and no VF as controls (group 4). We measured L1-L4, femoral neck and total hip areal bone mineral density (aBMD) by dual X-ray absorptiometry (DXA) (QDR 4500; Hologic, Waltham, MA) and calculated TBS from de-identified DXA L1-L4 scans by the TBS iNsight software (Medimaps, Geneva, Switzerland). The assessment of VF was performed by means of anteroposterior and left lateral standardized radiographs of the thoracic and lumbar spine. We calculated the FRAX® value in all subjects for the assessment of 10-year fracture risk for major and hip fractures. Forty-two subjects with L1-L4 T-score ≤ −3.0 had at least one VF (group 1), while 41 have no VF (group 2). Twenty-four subjects had L1-L4 T-score ≤ −1.0 and ≥ −2.4 and at least 3 VF (group 3). We observed significantly lower TBS values in group 1 and group 3 compared to group 2 (p < 0.001) and group 4 (p < 0.05). L1-L4 aBMD and TBS values were not significantly associated in all groups. Interestingly, TBS values were independently associated with the presence of VF (log odds ratio − 8, p < 0.001) but not with the number of VF by the stepwise regression analysis. Furthermore, when we applied the cut-off value of TBS associated with degraded microarchitecture and elevated fracture risk (< 1.23), only 52 % of the subjects had VF. The cut-off value of TBS below which VF could be predicted was calculated by the receiver operating characteristic curve analysis and was 1.13. Our study demonstrates an independent association between altered trabecular microarchitecture, assessed by TBS, and the occurrence of VF in postmenopausal women with osteoporosis. This association is significant for values of TBS lower than those reported by population-based studies. Cut-off values of TBS need further evaluation by specifically designed studies assessing disease- specific thresholds for fracture risk. • Trabecular bone score (TBS) is significantly impaired in women with postmenopausal osteoporosis • TBS is independently associated with the occurrence but not with the number of vertebral fractures in postmenopausal osteoporosis • Cut-off values of TBS used to identify elevated fracture risk are associated with the presence of vertebral fractures in roughly half of women with postmenopausal osteoporosis • There is a need for a disease- specific assessment of TBS cut-off values for identifying elevated risk for vertebral fracture [ABSTRACT FROM AUTHOR]

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) 2 D in regulating PTH secretion in healthy subjects. 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. 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) 2 D 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) 2 D 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. 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. • Under clinically stable conditions, vitamin D plays a significant role in regulating parathyroid hormone secretion. • There is a divergent behavior of PTH with aging between males and females. • The direct correlation between PTH and BMI is most probably mediated by 25(OH)D levels. [ABSTRACT FROM AUTHOR]