Occult urolithiasis in asymptomatic primary hyperparathyroidism.

OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. METHODS: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. RESULTS: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)2D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)2D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)2D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. CONCLUSION: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)2D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)2D suggests screening those with higher urinary calcium may be an appropriate approach.

Asymptomatic primary hyperparathyroidism.

The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term "asymptomatic primary hyperparathyroidism" was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease.

Normocalcemic primary hyperparathyroidism.

Primary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and elevated levels of parathyroid hormone (PTH). A newer presentation of primary hyperparathyroidism has been described over the past decade, in which PTH is elevated but serum calcium is consistently normal, in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency. Recognition of this phenotype of primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, supports a biphasic chronological time course in some individuals in which PTH levels are first elevated but serum calcium is normal, followed by the development of frank hypercalcemia. This review focuses on the available literature regarding this newly described phenotype of primary hyperparathyroidism.

Nontraditional manifestations of primary hyperparathyroidism.

Classical primary hyperparathyroidism (PHPT) was previously a multisystemic symptomatic disorder not only with overt skeletal and renal complications but also with neuropsychological, cardiovascular, gastrointestinal, and rheumatic effects. The presentation of PHPT has evolved, and today most patients are asymptomatic. Osteitis fibrosa cystica is rarely seen today, and nephrolithiasis is less common. Gastrointestinal and rheumatic symptoms are not part of the clinical spectrum of modern PHPT. It remains unclear whether neuropsychological symptoms and cardiovascular disease, neither of which are currently indications for recommending parathyroidectomy (PTX), are part of the modern phenotype of PHPT. A number of observational studies suggest that mild PHPT is associated with depression, decreased quality of life, and changes in cognition, but limited data from randomized controlled trials (RCTs) have not indicated consistent benefits after surgery. The increased cardiovascular morbidity and mortality in severe PHPT has not been definitively demonstrated in mild disease, although there is some evidence for more subtle cardiovascular abnormalities, such as increased vascular stiffness, among others. Results from observational studies that have assessed the effect of PTX on cardiovascular health have been conflicting. The single RCT in this area did not demonstrate that PTX was beneficial. Despite recent progress in these areas, more data from rigorously designed studies are needed to better inform the clinical management of patients with asymptomatic PHPT.

The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Management of Primary Hyperparathyroidism.

Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop.

The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the association of vitamin D deficiency and indices of mineral metabolism with subclinical carotid markers that predict cardiovascular events. METHODS: Two hundred three community-dwelling adults (Northern Manhattan Study; age, 68 ± 11; age range, 50 to 93 years) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone) and carotid ultrasound (plaque presence, number, maximal carotid plaque thickness, intima-media thickness). RESULTS: Adjusting for cardiovascular risk factors, plaque number was associated with phosphorus levels (ß=0.39 per 1-mg/dL increase; P=0.02) and calcium-phosphorus product (ß=0.36 per 10-U increase; P=0.03). In those with plaque (N=116 [57%]), the association of plaque number with phosphorus and calcium-phosphorus product persisted. In addition, 25-hydroxyvitamin D was inversely associated with both intima-media thickness (ß=-0.01 per 10-ng/mL increase; P=0.05) and maximal carotid plaque thickness (ß=-0.10 per 10-ng/mL increase; P=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25-hydroxyvitamin D accounted for 13% of the variance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures. CONCLUSIONS: After adjusting for cardiovascular risk factors and renal function, serum phosphorus and calcium-phosphorus product were associated with a greater burden of subclinical carotid atherosclerosis. Low 25-hydroxyvitamin D levels were associated with increased intima-media thickness and maximal carotid plaque thickness in those with plaque, and 25-hydroxyvitamin D contributed in a robust manner to the variance in both. These results confirm and extend data on the association of low vitamin D levels with subclinical carotid atherosclerosis. The precise nature of this association and the optimum levels of vitamin D for vascular health remain to be elucidated.

Nontraditional Aspects of Sporadic Primary Hyperparathyroidism.

Nontraditional aspects of primary hyperparathyroidism refer to the condition's rheumatic, gastrointestinal, cardiovascular, and neuropsychological effects. Although gastrointestinal and rheumatic symptomatology were features of classical primary hyperparathyroidism, they do not seem to be a part of the modern presentation of primary hyperparathyroidism. In contrast, neuropsychological symptoms such as altered mood and cognition, as well as cardiovascular disease, have been associated with the form of primary hyperparathyroidism seen today, but the relationship is not clearly causal. Evidence does not support reversibility after parathyroidectomy and therefore none of the nontraditional manifestations are considered sole indications for recommending surgery at this time.

Long-term Bone Loss and Deterioration of Microarchitecture After Gastric Bypass in African American and Latina Women.

CONTEXT: The prevalence of obesity is burgeoning among African American and Latina women; however, few studies investigating the skeletal effects of bariatric surgery have focused on these groups. OBJECTIVE: To investigate long-term skeletal changes following Roux-en-Y gastric bypass (RYGB) in African American and Latina women. DESIGN: Four-year prospective cohort study. PATIENTS: African American and Latina women presenting for RYGB (n = 17, mean age 44, body mass index 44 kg/m2) were followed annually for 4 years postoperatively. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the spine, hip, and forearm, and body composition. High-resolution peripheral quantitative computed tomography measured volumetric bone mineral density (vBMD) and microarchitecture. Individual trabecula segmentation-based morphological analysis assessed trabecular morphology and connectivity. RESULTS: Baseline DXA Z-Scores were normal. Weight decreased ~30% at Year 1, then stabilized. Parathyroid hormone (PTH) increased by 50% and 25-hydroxyvitamin D was stable. By Year 4, aBMD had declined at all sites, most substantially in the hip. There was significant, progressive loss of cortical and trabecular vBMD, deterioration of microarchitecture, and increased cortical porosity at both the radius and tibia over 4 years. There was loss of trabecular plates, loss of axially aligned trabeculae, and decreased trabecular connectivity. Whole bone stiffness and failure load declined. Risk factors for bone loss included greater weight loss, rise in PTH, and older age. CONCLUSIONS: African American and Latina women had substantial and progressive bone loss, deterioration of microarchitecture, and trabecular morphology following RYGB. Further studies are critical to understand the long-term skeletal consequences of bariatric surgery in this population.

Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

BACKGROUND: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. METHODS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. CONCLUSIONS: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after 8-10 yr, regular monitoring (serum calcium and three-site BMD) is essential in those followed without surgery. Patients may present with normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism). Data on the incidence and natural history of this phenotype are limited. 4) In the absence of kidney stones, data do not support the use of marked hypercalciuria (>10 mmol/d or 400 mg/d) as an indication for surgery for patients. 5) Patients with bone density T-score -2.5 or less at the lumbar spine, hip, or distal one third radius should have surgery.

Risk factors for vertebral fracture in primary hyperparathyroidism.

PURPOSE: Screening for vertebral fractures (VF) in primary hyperparathyroidism (PHPT) is recommended, but there are limited data regarding which patients are at greatest risk for VF. We evaluated risk factors for VF in PHPT. METHODS: This is a retrospective cross-sectional analysis of 117 participants with PHPT. We assessed Grades 2 and 3 VF by vertebral fracture assessment (VFA) and the association of VF with the trabecular bone score (TBS), other skeletal parameters and clinical risk factors. VFA was performed only in those who met National Osteoporosis Foundation criteria for VFA screening. RESULTS: T-scores were in the osteopenic range and TBS was degraded. Overall VF rate based on VFA or other imaging was 12.8%. Serum PTH, calcium and TBS were not associated with VF. Those with VF were older (p = 0.04), had worse renal function (p = 0.04), were more likely to have received osteoporosis treatment (p = 0.03), and tended to have had a prior fracture (p = 0.06). T-scores did not differ by fracture status at any skeletal site. Those with VF had nine times the odds of osteoporosis at the hip (95% CI 2.4-34.5), but this risk factor had low sensitivity (46.7%) for VF. Hip T-score < -2.6, Age > 78.6 years, and GFR < 58.8 ml/min/1.73 m2 (thresholds maximizing sensitivity and specificity) had areas under the curve of 0.60-0.67 for VF (all p < 0.05) and low sensitivity. Findings were similar when analyses were limited to women. CONCLUSIONS: In PHPT, VF risk factors included older age, prior fracture, worse renal function and osteoporosis at the hip, but not osteoporosis at other sites, TBS or biochemical indices of PHPT. Since identified risk factors had low sensitivity and were generally inaccurate for categorizing those with VF, the data do not support limiting screening to PHPT patients with these specific VF risk factors.

The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years.

CONTEXT: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue. OBJECTIVE: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr. DESIGN: The study had an observational design. SETTING: The setting was a referral center. PATIENTS: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic. INTERVENTION: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery. MAIN OUTCOME MEASURE: BMD was measured. RESULTS: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 +/- 3% (mean +/- sem; P < 0.05) at the femoral neck, and 35 +/- 5%; P < 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr. CONCLUSIONS: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.

Bone quality determined by Fourier transform infrared imaging analysis in mild primary hyperparathyroidism.

CONTEXT: Mild primary hyperparathyroidism (PHPT) is characterized by asymptomatic hypercalcemia, most commonly in the absence of classical signs and symptoms. Hence, there is need to characterize this disorder with particular attention to the skeleton. DESIGN: We determined the ratio of pyridinium and dehydrodihydroxylysinonorleucine collagen cross-links in 46 iliac crest bone biopsies from patients with PHPT (14 men, aged 28-68 yr; 32 women, aged 26-74 yr) by Fourier transform infrared imaging. The results were compared with previously reported collagen cross-links ratio determined in iliac crest biopsies from normal subjects. RESULTS: PHPT patients exhibited significantly lower pyridinium to dehydrodihydroxylysinonorleucine collagen cross-links ratio, compared with normal controls. Parathyroidectomy restored values to those comparable with normal controls. Moreover, the differences among PHPT subjects were gender dependent, with female PHPT patients having a statistically significant lower ratio, compared with either male PHPT patients or normal controls. Comparison of the obtained outcomes with histomorphometry showed that the collagen cross-link ratio was strongly correlated with rate of bone formation, and mineralizing surface, in individual patients. This ratio was also correlated with bone mineralization density distribution parameters obtained in the same patients. The strongest correlations were with bone mineralization density distribution variables reflecting heterogeneity of mineralization and primary mineralization parameters. CONCLUSIONS: The results are consistent with the high turnover state manifested in PHPT patients. Reduced collagen cross-link ratio in patients with PHPT would be expected to reduce the stiffness of bone tissue. These observations provide a more complete assessment of bone material properties in this disorder.

Parathyroid hormone and the cardiovascular system.

The classical actions of parathyroid hormone (PTH) are well recognized, but its effects on other target tissues, such as the cardiovascular system, are less appreciated. Several studies have evaluated the effects of PTH in patients with primary hyperparathyroidism in order to understand potential cardiovascular effects in terms of hypertension, cardiovascular mortality, left ventricular function, and endothelial function. We review these studies and evaluate the cellular mechanisms that may affect these outcomes.

Primary hyperparathyroidism.

In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a common endocrine disorder that is characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Most often, the presentation of PHPT is asymptomatic in regions of the world where serum levels of calcium are routinely measured. In addition to mild hypercalcaemia, PHPT can manifest with osteoporosis and hypercalciuria as well as with vertebral fractures and nephrolithiasis, both of which can be asymptomatic. Other clinical forms of PHPT, such as classical disease and normocalcaemic PHPT, are less common. Parathyroidectomy, the only curative treatment for PHPT, is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. Various medical therapies can increase BMD or reduce serum levels of calcium, but no single drug can do both. More data are needed regarding the neuropsychological manifestations of PHPT and the pathogenetic mechanisms leading to sporadic PHPT, as well as on risk factors for complications of the disorder. Future work that advances our knowledge in these areas will improve the management of the disorder.

Classical complications of primary hyperparathyroidism.

Traditionally, classical complications of primary hyperparathyroidism are mainly represented by skeletal, kidney and gastrointestinal involvement. The old picture of osteitis fibrosa cystica is no longer commonly seen, at least in the western world. However, new imagining techniques have highlighted deterioration of skeletal tissue in patients with primary hyperparathyroidism not captured by traditional DXA measurement. Concerning the kidney, the most common consequences of excessive parathyroid hormone secretion are hypercalciuria and kidney stones; however, the exact pathogenesis of urinary stone formation is still unknown. The 2013 International Congress on the management of Asymptomatic Primary Hyperparathyroidism, emphasized the role of imaging techniques for early discovery of both skeletal and renal complications in asymptomatic patients. Gastrointestinal manifestations include acid-peptic disease, constipation, pancreatitis and gall stone disease. More studies are needed in this area to find the exact pathophysiological mechanism underlying these manifestations and the effect of parathyroid surgery.

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.

New observations on bone quality in mild primary hyperparathyroidism as determined by quantitative backscattered electron imaging.

UNLABELLED: Bone mineralization density distribution, an important aspect of bone material quality, was determined in mild primary hyperparathyroidism using quantitative backscattered electron imaging. A strong correlation between bone turnover status and degree and heterogeneity of mineralization was found. Further studies are needed before we can draw conclusions about fracture risk in this disorder. INTRODUCTION: Mild primary hyperparathyroidism (PHPT) is best characterized by asymptomatic hypercalcemia, most commonly in the absence of classical signs and symptoms. Hence, there is need to characterize this disorder with particular attention to the skeleton. MATERIALS AND METHODS: We analyzed bone mineralization density distribution (BMDD) in iliac crest bone biopsies from patients with PHPT in 51 subjects (16 men, 28-68 years of age; 35 women, 26-74 years of age) by quantitative backscattered electron imaging (qBEI). The BMDD variables quantified are as follows: Ca(MEAN), the weighted mean calcium concentration; Ca(PEAK), the most frequent Ca concentration; Ca(WIDTH), the width of the distribution, a measure of the mineralization homogeneity; Ca(LOW), the percentage of bone area that is mineralized below the fifth percentile in the reference range. The results were compared with a reference range that we have previously established. RESULTS: The greatest differences were found in Ca(WIDTH) (+15.7%, p<0.0001) and Ca(LOW) (+44.7%, p<0001), both of which were significantly higher in PHPT than control. Ca(MEAN) was significantly lower (-2.5%, p<0.0001) in PHPT compared with controls. These differences were reversed in seven patients who underwent parathyroidectomy. Ca(MEAN) and Ca(PEAK) variables were negatively, whereas Ca(WIDTH) and Ca(LOW) were positively, correlated with dynamic variables of bone formation: mineralizing surface and bone formation rate as determined by histomorphometry. (r = +/-0.3-0.8; p=0.05-0.0001). These results, which represent the first BMDD measurements in mild PHPT using qBEI, show a reduction in the average mineralization density and an increase in the heterogeneity of the degree of mineralization. These changes correlate significantly with the bone turnover rate. CONCLUSIONS: The results are consistent with our previous observations of increased bone turnover in this disease, and consequently, reduced mean age of bone tissue. Reduced mineralization density in patients with PHPT would be expected to reduce the stiffness of bone tissue. These observations are relevant to considerations of fracture risk in PHPT.