Classical and Nonclassical Manifestations of Primary Hyperparathyroidism.

This narrative review summarizes data on classical and nonclassical manifestations of primary hyperparathyroidism (PHPT). It is based on a rigorous literature search, inclusive of a Medline search for systematic reviews from 1940 to December 2020, coupled with a targeted search for original publications, covering four databases, from January 2013-December 2020, and relevant articles from authors' libraries. We present the most recent information, identify knowledge gaps, and suggest a research agenda. The shift in the presentation of PHPT from a predominantly symptomatic to an asymptomatic disease, with its varied manifestations, has presented several challenges. Subclinical nephrolithiasis and vertebral fractures are common in patients with asymptomatic disease. The natural history of asymptomatic PHPT with no end organ damage at diagnosis is unclear. Some observational and cross-sectional studies continue to show associations between PHPT and cardiovascular and neuropsychological abnormalities, among the different disease phenotypes. Their causal relationship is uncertain. Limited new data are available on the natural history of skeletal, renal, cardiovascular, neuropsychological, and neuromuscular manifestations and quality of life. Normocalcemic PHPT (NPHPT) is often diagnosed without the fulfillment of rigorous criteria. Randomized clinical trials have not demonstrated a consistent long-term benefit of parathyroidectomy (PTX) versus observation on nonclassical manifestations. We propose further refining the definition of asymptomatic disease, into two phenotypes: one without and one with evidence of target organ involvement, upon the standard evaluation detailed in our recommendations. Each of these phenotypes can present with or without non-classical manifestations. We propose multiple albumin-adjusted serum calcium determinations (albumin-adjusted and ionized) and exclusion of all secondary causes of high parathyroid hormone (PTH) when establishing the diagnosis of NPHPT. Refining the definition of asymptomatic disease into the phenotypes proposed will afford insights into their natural history and response to interventions. This would also pave the way for the development of evidence-based guidance and recommendations. © 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).

No evidence of mineralization abnormalities in iliac bone of premenopausal women with type 2 diabetes mellitus.

OBJECTIVES: Patients with type-2 diabetes mellitus (T2DM) have increased risk for bone fractures which points towards impaired bone quality. METHODS: We measured bone mineralization density distribution (BMDD) and osteocyte lacunae section (OLS) characteristics based on quantitative backscattered electron images of transiliac biopsy samples from n=26 premenopausal women with T2DM. Outcomes were compared to those from reference cohorts as well as between T2DM subgroups defined by clinical characteristics. RESULTS: Comparison to references did not reveal any differences in BMDD (all p>0.05) but a lowered OLS-density in cancellous bone in T2DM (-14.9%, p<0.001). Neither BMDD nor OLS-characteristics differed in T2DM subgroups defined by HbA1c (<7% versus >7%). The average degree of bone mineralization (CaMean) was higher (0.44 wt%Ca in T2DM, 0.30 wt%Ca in reference) and consistently the calcium concentration between the tetracycline double labels (CaYoung) was higher (0.76 wt%Ca, all p<0.001) in cancellous versus cortical bone. CONCLUSIONS: Our findings suggest that bone matrix mineralization was neither affected by the presence nor by the glycemic control of T2DM in our study cohort. The intra-individual differences between cancellous and cortical bone mineralization gave evidence for differences in the time course of the early mineralization process in these compartments in general.

Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus

ABSTRACT Objective: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). Materials and methods: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. Results: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). Conclusion: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). METHODS: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. RESULTS: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). CONCLUSION: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Bone tissue material composition is compromised in premenopausal women with Type 2 diabetes.

Type 2 diabetes mellitus (T2DM) patients are at an increased risk of fracture despite normal to high bone mineral density (BMD) values. In this cross-sectional study we establish bone compositional properties in tetracycline labeled iliac crest biopsies from premenopausal women diagnosed with T2DM (N = 26). Within group comparisons were made as a function of tissue age (TA), presence of chronic complications (CC), glycosylated haemoglobin (HbA1c) levels, and morphometric fracture (MFx). We also compared these data at actively trabecular bone forming surfaces against sex- and age-matched healthy controls (N = 32). The bone quality indices determined by Raman microspectroscopic analysis were: mineral/matrix (MM), tissue water content (nanoporosity; NanoP), mineral maturity/crystallinity (MMC), and glycosaminoglycan (GAG), pyridinoline (Pyd), N-(carboxymethyl)lysine (CML), and pentosidine (PEN) content. Within the T2DM group, at the oldest tissue, CML and PEN contents were significantly elevated in the cancellous compared to cortical compartment. The outcomes were not dependent on MFx. On the other hand, both were significantly elevated in patients with CC, as well as those with HbA1c levels > 7%. At actively forming surfaces, the cortical compartment had higher NanoP compared to cancellous. Still within the T2DM group, patients with MFx had significantly elevated MM and GAGs compared to the ones that did not. At actively forming trabecular surfaces, compared to healthy women, T2DM patients had elevated GAGs content and MMC. The results of this study indicate increased AGEs in those with poor glycation control and chronic complications. Additionally, T2DM patients had elevated MMC and decreased GAGs content compared to healthy controls. These alterations may be contributing to the T2DM inherent elevated fracture risk and suggest a role for hyperglycemia on bone quality.

Trabecular bone score (TBS) and bone mineral density in patients with long-term therapy with warfarin.

In this study, we compared patients using the anticoagulant warfarin for more than a year with a control group with similar characteristics but without using the drug. We demonstrated worse BMD and bone quality by trabecular bone score (TBS) in patients using warfarin for more than 1 year. PURPOSE: Evaluate the bone mineral density (BMD) and the trabecular bone score (TBS) of patients taking warfarin for more than 1 year compared with a control group. METHODS: Male patients aged 25-65 years in warfarin use for more than 1 year were included. Patients answered a questionnaire regarding lifestyle habits and realized a dual X-ray densitometry (DXA) (lumbar spine and hip), and TBS was evaluated. RESULTS: From the 96 patients invited, 33 patients accepted to participate and comprised the warfarin group (WG), and 3 were excluded. The control group (CG) was composed of 21 individuals matched by age and race. The mean age of WG was 57.0 ± 7.6 and in the CG 54.0 ± 10.6 years (p = 0.095). The BMD in WG was lower than that in the CG in all sites (spine p < 0.001, total hip p = 0.001, and femoral neck p = 0.005). A longer time of warfarin use increased the likelihood of having low BMD (OR = 1.239, CI 1.064-1.674, p = 0.01), whereas high BMI decreased it (OR = 0.732, CI 0.533-0.918, p = 0.03). The TBS was lower in WG than the CG (p = 0.04). Lower TBS was associated with hypertension in both groups and to the hip BMD (neck and total) (p < 0.005) in the WG. In the multivariate analysis, only hypertension (- 0.10, CI - 0.17 to - 0.03, p = 0.008) and total hip BMD ( 0.26, CI 0.07-0.46, p = 0.009) influenced TBS. CONCLUSION: We demonstrated an association between worsening of BMD and bone quality in patients taking warfarin for more than 1 year.

Primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a condition that affects calcium metabolism due to parathyroid hormone (PTH) hypersecretion leading to hypercalcemia. Manifestations have changed over time, from a symptomatic disease with bone pain, fractures, nephrolithiasis, and muscle weakness, to a condition that is mainly asymptomatic (80-90%). Typical symptoms and signs occur in the bones and kidneys and atypical manifestations are cardiovascular, neuropsychiatric and cognitive, neuromuscular, rheumatological, and gastrointestinal. Diagnosis occurs, in most cases, in asymptomatic patients by a routine calcium measurement with corrected high total calcium associated with high or inappropriately abnormal PTH. If indicated, a search for the location of the involved parathyroid gland should be performed with ultrasound, scintigraphy, or 4D CT. Parathyroidectomy is the gold standard treatment. If surgery cannot be performed, clinical management is indicated. Surgical indications are osteoporosis, hypercalciuria, spine fractures, age <50 years, calcemic values above 1.0 mg/dL threshold value, creatinine clearance ≤60 mL/min, and nephrolithiasis or nephrocalcinosis.

Template for the laboratorys report of 25-hydroxyvitamin D: recommendations form the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) and the Brazilian Society of Endocrinology and Metabolism (SBEM) / Modelo de laudo laboratorial para 25-hidroxivitamina D: recomendações da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)

ABSTRACT The Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) and the Brazilian Society of Endocrinology and Metabolism (SBEM) recommend a new template for laboratory reports of 25-hydroxyvitamin D: deficiency < 20 ng/ml; normal values for the general population between 20-60 ng/ml; ideal values for at-risk population between 30-60 ng/ml; e risk of toxicity > 100 ng/ml.

RESUMEN La Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) y la Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) sugieren un nuevo modelo de informe de laboratorio para 25-hidroxivitamina D: deficiencia < 20 ng/ml; valores normales para la población general entre 20 y 60 ng/ml; valores ideales para la población de riesgo entre 30 y 60 ng/ml; riesgo de intoxicación > 100 ng/ml.

RESUMO A Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) e a Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) recomendam um novo modelo de laudo laboratorial para 25-hidroxivitamina D: deficiência < 20 ng/ml; valores normais para a população geral entre 20 e 60 ng/ml; valores ideais para população de risco entre 30 e 60 ng/ml; e risco de intoxicação > 100 ng/ml.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women.

OBJECTIVE: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. SUBJECTS AND METHODS: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. RESULTS: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). CONCLUSION: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women

ABSTRACT Objective: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. Subjects and methods: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. Results: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). Conclusion: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Self-report of psychological symptoms in hypoparathyroidism patients on conventional therapy.

OBJECTIVE: Hypoparathyroidism is characterized by parathyroid hormone deficiency and hypocalcemia. It has been demonstrated that these patients may also present psychiatric symptoms and decrease of quality of life. The aims of this study were to evaluate the presence of psychopathological symptoms in a cohort of patients with hypoparathyroidism and compare to a control group. SUBJECTS AND METHODS: Patients were submitted to a cross-sectional Symptom Checklist-90-R (SCL-90-R) questionnaire that evaluates psychopathological symptoms by means of the Global Severity Index (GSI), Positive Symptoms Total (PST) and Positive Symptom Distress Index (PSDI). A score based in the positive symptoms was calculated (T-score). The test group was composed of patients with hypoparathyroidism, and control by thyroidectomized patients without hypoparathyroidism. A correlation between the presence of psychological symptoms and clinical features was analyzed. RESULTS: The study included 57 patients with a mean age of 51.1 ± 16.4 years; 20 as a control and 37, test group. There were no differences between groups regarding gender, mean age and age at diagnose. Hypoparathyroidism patients presented higher GSI index than the control group (p = 0.038). Mean T-score of the test group was as elevated as 58.2 ± 5.3 (reference range < 55). No correlation of the number of psychological symptoms to clinical and laboratorial parameters was observed. CONCLUSION: Patients with hypoparathyroidism attending our outpatient clinics presented an increase in the number of self-report of psychological symptoms when compared with a control group. However, no correlation with hypocalcemia and clinical parameters was observed. Future studies are necessary to evaluated if the absence of PTH play a role on it.

Self-report of psychological symptoms in hypoparathyroidism patients on conventional therapy

ABSTRACT Objective: Hypoparathyroidism is characterized by parathyroid hormone deficiency and hypocalcemia. It has been demonstrated that these patients may also present psychiatric symptoms and decrease of quality of life. The aims of this study were to evaluate the presence of psychopathological symptoms in a cohort of patients with hypoparathyroidism and compare to a control group. Subjects and methods: Patients were submitted to a cross-sectional Symptom Checklist-90-R (SCL-90-R) questionnaire that evaluates psychopathological symptoms by means of the Global Severity Index (GSI), Positive Symptoms Total (PST) and Positive Symptom Distress Index (PSDI). A score based in the positive symptoms was calculated (T-score). The test group was composed of patients with hypoparathyroidism, and control by thyroidectomized patients without hypoparathyroidism. A correlation between the presence of psychological symptoms and clinical features was analyzed. Results: The study included 57 patients with a mean age of 51.1 ± 16.4 years; 20 as a control and 37, test group. There were no differences between groups regarding gender, mean age and age at diagnose. Hypoparathyroidism patients presented higher GSI index than the control group (p = 0.038). Mean T-score of the test group was as elevated as 58.2 ± 5.3 (reference range < 55). No correlation of the number of psychological symptoms to clinical and laboratorial parameters was observed. Conclusion: Patients with hypoparathyroidism attending our outpatient clinics presented an increase in the number of self-report of psychological symptoms when compared with a control group. However, no correlation with hypocalcemia and clinical parameters was observed. Future studies are necessary to evaluated if the absence of PTH play a role on it.

Consensus - reference ranges of vitamin D [25(OH)D] from the Brazilian medical societies. Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) and Brazilian Society of Endocrinology and Metabolism (SBEM) / Posicionamento oficial da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) sobre intervalos de referência da vitamina D [25(OH)D]

ABSTRACT Introduction: Vitamin D is considered a pre-hormone and plays a crucial role in calcium homeostasis and, consequently, in bone health. The best source of vitamin D is the skin in response to sunlight. Only small amounts of this vitamin are found in some foods (especially fatty fish), which makes availability of vitamin D in the diet limited. Brazilian population studies show that the prevalence of hypovitaminosis D in our country is high. Objective: To define the reference intervals for vitamin D [25(OH)D]. Discussion: Consensus of specialists - literature review. Conclusion: The standardization of reference intervals is fundamental for the correct diagnosis and treatment of hypovitaminosis D.

RESUMO Introdução: A vitamina D é considerada um pré-hormônio e apresenta papel crucial na homeostase do cálcio e, consequentemente, na saúde óssea. A maior fonte de vitamina D é a pele, em resposta à luz solar. Apenas pequenas quantidades dessa vitamina são encontradas em alguns alimentos (especialmente peixes gordurosos), o que faz com que a disponibilidade da vitamina D na dieta seja limitada. Estudos populacionais brasileiros demonstram que a prevalência da hipovitaminose D no nosso país é elevada. Objetivo: Definição dos intervalos de referência para vitamina D [25(OH)D]. Discussão: Consenso de especialistas - revisão da literatura. Conclusão: A padronização dos intervalos de referência é fundamental para o correto diagnóstico e tratamento da hipovitaminose D.

Stress Fractures: Concepts and Therapeutics.

Context: Stress fractures are repetitive use injuries in which recurrent strains lead to material fatigue and microarchitectural discontinuities. They account for up to 20% of athletic injuries, more often in women and in the setting of track-and-field events. In women, menstrual disturbances, low body mass index, low energy intake, and sometimes low bone mass, may be contributing factors. There are no standard protocols for evaluation or management of stress fractures. Evidence Acquisition: Available literature published in English was retrieved using the following terms: stress fractures; fractures; osteoporosis, athletes, premenopausal women, and athletic triad; through PubMed. Reviews, original reports, and case reports were all included. Evidence Synthesis: Despite lack of consistency among the publications, a phenotype emerges, namely of individuals whose bone mineral density is reduced along with low intake of dietary calcium and low circulating levels of 25-hydroxy vitamin D. Limited experience suggests that calcium and vitamin D supplementation might be helpful. Bisphosphonates or teriparatide may accelerate fracture healing in special circumstances. Conclusions: Most individuals who experience a stress fracture are young and healthy and do not appear to have an underlying metabolic bone disease. On the other hand, the presence of low bone mass and hormonal disturbances in some afflicted individuals might identify a cohort who needs endocrinological attention. Prospective, well-designed studies of stress fractures are needed to elucidate further underlying pathophysiological elements that predispose such individuals. Guidelines for prevention and treatment may follow from such well-controlled studies.

Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: The ACTIVE phase 3 trial.

There are a number of effective treatments for osteoporosis but most are in the antiresorptive class of compounds. Abaloparatide-SC is a new osteoanabolic agent, which increased bone mineral density and lowered the risk of osteoporosis-related fractures in the phase 3 ACTIVE trial. The objective of this report is to describe the effects of abaloparatide-SC 80µg on bone histology and histomorphometry in iliac crest bone biopsies from this trial in which participants were randomized to receive blinded daily subcutaneous injections of placebo or abaloparatide-SC 80µg/d or open-label teriparatide 20µg/d for 18months. Iliac crest bone biopsies were obtained between 12 and 18months. Qualitative histological analysis of biopsies from abaloparatide-SC-treated patients revealed normal bone microarchitecture without evidence of adverse effects on mineralization or on the formation of normal lamellar bone. There were no bone marrow abnormalities, marrow fibrosis nor was there presence of excess osteoid or woven bone. There were few significant differences among the three treatment groups in a standard panel of static and dynamic histomorphometric indices. The mineral apposition rate was higher in the teriparatide-treated group than in the placebo-treated group. The eroded surface was lower in the abaloparatide-SC-treated group than in the placebo-treated group. Cortical porosity was higher in both the abaloparatide-SC- and the teriparatide-treated groups than in the placebo-treated group. We conclude that histological and histomorphometric analysis of iliac crest bone biopsies from subjects who were treated for up to 18months with abaloparatide-SC showed no evidence of concern for bone safety. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01343004.

Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD) Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline Content at Actively Bone-Forming Trabecular Surfaces.

Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research.

Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications.

OBJECTIVES: To identify a clinical profile and laboratory findings of a cohort of hypoparathyroidism patients and determine the prevalence and predictors for renal abnormalities. MATERIALS AND METHODS: Data from medical records of five different visits were obtained, focusing on therapeutic doses of calcium and vitamin D, on laboratory tests and renal ultrasonography (USG). RESULTS: Fifty-five patients were identified, 42 females and 13 males; mean age of 44.5 and average time of the disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum calcium and creatinine increased between the first and last visits (p < 0.001 and p < 0.05, respectively); and serum levels of phosphate decreased during the same period (p < 0.001). Out of the 55 patients, 40 had USG, and 10 (25%) presented with kidney calcifications. There was no significant difference in the amount of calcium and vitamin D doses among patients with kidney calcifications and others. No correlation between serum and urinary levels of calcium and the presence of calcification was found. Urinary calcium excretion in 24h was significantly higher in patients with kidney calcification (3.3 mg/kg/d) than in those without calcification (1.8 mg/kg/d) (p < 0.05). CONCLUSIONS: The reduction of hypocalcemia and hyperphosphatemia suggest an effectiveness of the treatment, and the increase in serum creatinine demonstrates an impairment of renal function during follow-up. Kidney calcifications were prevalent in this cohort, and higher urinary calcium excretion, even if still within the normal range, was associated with development of calcification. These findings suggest that lower rates of urinary calcium excretion should be aimed for in the management of hypoparathyroidism.

Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

ABSTRACT Objectives To identify a clinical profile and laboratory findings of a cohort of hypoparathyroidism patients and determine the prevalence and predictors for renal abnormalities. Materials and methods Data from medical records of five different visits were obtained, focusing on therapeutic doses of calcium and vitamin D, on laboratory tests and renal ultrasonography (USG). Results Fifty-five patients were identified, 42 females and 13 males; mean age of 44.5 and average time of the disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum calcium and creatinine increased between the first and last visits (p < 0.001 and p < 0.05, respectively); and serum levels of phosphate decreased during the same period (p < 0.001). Out of the 55 patients, 40 had USG, and 10 (25%) presented with kidney calcifications. There was no significant difference in the amount of calcium and vitamin D doses among patients with kidney calcifications and others. No correlation between serum and urinary levels of calcium and the presence of calcification was found. Urinary calcium excretion in 24h was significantly higher in patients with kidney calcification (3.3 mg/kg/d) than in those without calcification (1.8 mg/kg/d) (p < 0.05). Conclusions The reduction of hypocalcemia and hyperphosphatemia suggest an effectiveness of the treatment, and the increase in serum creatinine demonstrates an impairment of renal function during follow-up. Kidney calcifications were prevalent in this cohort, and higher urinary calcium excretion, even if still within the normal range, was associated with development of calcification. These findings suggest that lower rates of urinary calcium excretion should be aimed for in the management of hypoparathyroidism.

Skeletal Implications of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with numerous comorbidities, among which osteoporosis is of high significance. Low bone mass and the occurrence of fragility fractures is a common finding in patients with COPD. Typical risk factors related directly or indirectly to these skeletal complications include systemic inflammation, tobacco smoking, vitamin D deficiency, and treatment with oral or inhaled corticosteroids. In particular, treatment with glucocorticoids appears to be a strong contributor to bone changes in COPD, but does not fully account for all skeletal complications. Additional to the effects of COPD on bone mass, there is evidence for COPD-related changes in bone microstructure and material properties. This review summarizes the clinical outcomes of low bone mass and increased fracture risk, and reports on recent observations in bone tissue and material in COPD patients.

New insights on diabetes and bone metabolism.

Diabetes mellitus is a common chronic metabolic disease worldwide whose prevalence has increased during the last decades. Besides its more commonly recognized complications, such as macrovascular disease, retinopathy, nephropathy and neuropathy, diabetes related bone disease has gained growing attention. Diabetic patients are more prone to fracture than the general population as well as to low turnover bone disease in the chronic kidney disease setting. In this review, we discuss the relationship between diabetes and bone as well as the pathogenesis of bone fragility in T2D.