High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism.

INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. OBJECTIVE: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. METHODS AND RESULTS: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11-65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. CONCLUSION: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.

Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes.

CONTEXT: Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D have not been clearly established. OBJECTIVE: The objective of the study was to determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a tertiary medical center. PATIENTS: Sixteen postmenopausal women with T2D and 19 matched controls participated in the study. MAIN OUTCOME MEASURES: Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF, and circulating bone turnover markers were measured. RESULTS: BMSi was reduced by 9.2% in T2D (P = .02) and was inversely associated with the duration of T2D (r = -0.68, P = .004). Increased SAF was associated with reduced BMSi (r = -0.65, P = .006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r = -0.63, P = .01) in T2D, whereas no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (P = .03). CONCLUSIONS: Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.