Unmeasurable low vitamin D levels caused by a novel, homozygote loss-of-function variant in the group-specific component gene.

A 29-year-old female, born to consanguineous parents, was found with unmeasurable levels of vitamin D (<10 nmol/L) after routine biochemical screening during her first pregnancy. She did not respond to either oral or intramuscular vitamin D supplementation and was an otherwise healthy young woman, with no signs of rickets, osteomalacia, osteoporosis, or secondary hyperparathyroidism. Western blot analysis revealed total lack of vitamin D binding protein, and next generation sequencing confirmed a novel, pathogenic homozygote loss-of-function mutation in exon 13 of the group-specific component gene, that encodes the poly A tail for vitamin D binding protein. She was therefore diagnosed with hereditary DBP deficiency, and vitamin D supplementation was diminished to life-long regular vitamin D supplementation (25 µg per day). This case is extremely interesting, as it expands our knowledge of vitamin D physiology and supports the free hormone hypothesis, given that the patient was asymptomatic despite no measurable levels of vitamin D.

Hypoparathyroidism: changes in brain structure, cognitive impairment, and reduced quality of life.

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system-including subjective feelings of confusion, a reduced ability to focus and think clearly(i.e., "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires-the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of MRI images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus-and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning.

Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of Parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog". We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and Magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog". Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure.

Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1-84).

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1-84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1-84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 µg rhPTH(1-84) a day (n = 21) (PTH) or similar placebo (n = 21) (PLB) for 6 months as add-on to conventional therapy. This was followed by an open-label extension, where patients extended their rhPTH(1-84) (PTH) (n = 5), continued conventional treatment (CON) (n = 5), or withdrew from rhPTH(1-84) and resumed conventional therapy (PTHw) for an additional 24 months (n = 8). Bone biopsies were collected at months 6 (n = 42) and 30 (n = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH-treated patients. In the rhPTH(1-84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1-84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A Critical Role of the Bone Marrow Envelope in Human Bone Remodeling.

Proper bone remodeling depends not only on a team of bone-resorbing osteoclasts and bone-forming osteoblasts. It also depends on the site-specific delivery of a large amount of osteoblast lineage cells to the bone remodeling site. How this delivery occurs is poorly known. Here, we gained insight into this mechanism by analyzing the distribution of markers of osteoblastogenesis on bone surfaces and in their bone marrow neighborhood in human cancellous bone. We found a CD271-positive/PDGFß-R-positive cell layer surrounding the bone marrow that provides osteoblastogenic potential along all bone surfaces, whether quiescent or remodeling. This bone marrow envelope cell layer takes the appearance of a canopy above remodeling sites, where it then also shows an upregulation of the proliferation marker Ki67, smooth muscle actin (SMA), tenascin C, fibronectin, and MMP13. This indicates that the canopy is a region of the bone marrow envelope where early markers of osteoblastogenesis are activated concurrently with initiation of bone remodeling. Importantly, the high proliferation index in the canopy is not associated with increasing cell densities at the canopy level, but it is at the bone surface level, thereby supporting delivery of cells from the canopy to the bone surface. This delivery route explains why lack of canopies was previously found to coincide with lack of bone formation, and fits current knowledge on the canopies as a target for regulators of bone remodeling. We conclude that the coordination of bone marrow envelope activities and bone surface activities allows integrating osteoblastogenesis and bone remodeling into the same functional unit, and propose that the bone marrow envelope is critical for preserving bone health. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism.

Chronic hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone. This rare disorder is associated with a variety of complications. The prevalence, incidence, mortality, financial burden, and epidemiology of complications of this disorder are not well understood. This narrative review summarizes current information on the epidemiology and complications of chronic hypoparathyroidism. The reported prevalence of chronic hypoparathyroidism ranges from 6.4-37/100,000, and the incidence is reported to be 0.8-2.3/100,000/year. Mortality is not increased in studies from Denmark or South Korea but was increased in studies from Scotland and Sweden. The financial burden of this disorder is substantial because of increased health care resource utilization in two studies but not well quantitated. Recognized complications include hypercalciuria, nephrocalcinosis, kidney stones, and chronic kidney disease; low bone turnover and possibly upper extremity fractures; cardiac and vascular calcifications; basal ganglia calcifications, cataracts, infections, neuropsychiatric complications, and difficulties with pregnancy. This review concludes that chronic hypoparathyroidism is a rare disorder associated with significant morbidity that may not increase overall mortality but is associated with a substantial financial burden. © 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).

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.

Human hematopoietic microenvironments.

Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- "hematopoietic stem cells and multipotent progenitors" and a population of CD34+/CD38+ "progenitors" based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other "hematopoietic stem cells and multipotent progenitors" and other "progenitors") within 30 µm of "hematopoietic stem cells and multipotent progenitors", "progenitors", and "random cell profiles". We show that the microenvironment of the "hematopoietic stem cells and multipotent progenitors" is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the "progenitors" is significantly enriched in capillaries, other "progenitors", bone surfaces and arteries.

Determinants of hypercalciuria and renal calcifications in chronic hypoparathyroidism: A cross-sectional study.

OBJECTIVE: Hypercalciuria, impaired kidney function and renal calcifications are common in chronic hypoparathyroidism (HypoPT). We aimed to study associations between indices of known importance to the kidney in HypoPT by hypothesizing adverse effects of hypercalciuria on renal outcomes. DESIGN: We used cross-sectional design. PATIENTS: We identified all patients followed for chronic HypoPT at our department and who had been examined by a 24-h urine collection for measurement of renal calcium excretion (24 h U-Ca). MEASUREMENTS: By chart review, we identified additional biochemistry measured in close connection with the collection of urine, as well as demographic, treatments and anthropometrics. RESULTS: The 166 included patients (79.5% females) had a high prevalence of hypercalciuria (65.7%). In multiple adjusted analyses, hypercalciuria was in an independent manner inversely associated with (residual) levels of plasma PTH and positively associated with levels of 1,25-dihydroxyvitamin D and ionized calcium as well as 24 h U-phosphate, gender, and etiology (surgical vs. non-surgical). Overall, this model explained 54% (p < .001) of the variation in the presence of hypercalciuria. Chronic kidney disease stage three or above was present in 18.3% of the patients, and 42.6% of the 54 patients examined by renal imaging had renal calcifications. However, neither renal function nor renal calcifications were associated with 24 h U-Ca. CONCLUSIONS: Hypercalciuria, impaired renal function and renal calcifications are common in hypoparathyroidism. Hypercalciuria is to a large extent explained by indices of known physiological importance to 24 h U-Ca. However, in the present study, a high renal calcium excretion did not explain renal impairment or kidney calcifications.

Lower Leg Arterial Calcifications Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Hypoparathyroid and Pseudohypoparathyroid Patients.

Hypoparathyroidism (HypoPT) and pseudohypoparathyroidism (PHP) are diseases with abnormal calcium and phosphate homeostasis and low and high PTH levels, respectively. It has been hypothesized that this could dispose to vascular calcifications and thereby perhaps also cardiovascular morbidity. The aim of this study was to assess lower leg arterial calcifications (LLAC) in patients with HypoPT or PHP. Using a cross-sectional design, we measured the LLAC using a high-resolution peripheral quantitative computed tomography (HR-pQCT) scanner in 72 patients with HypoPT and 25 patients with PHP and compared them with findings in 61 controls. LLAC were found in only two (3%) of the controls. Compared to the controls, LLAC were significantly more prevalent in patients with HypoPT (N = 12, [17%], p < 0.01) and PHP (N = 4, [16%], p < 0.04). Compared to the patients without calcifications, patients with calcifications had higher plasma calcium levels and a lower eGFR, as well as they were older and more often males. Plasma phosphate levels and the calcium-phosphate product were not associated with LLAC. In conclusion, we found that HypoPT and PHP are associated with an increased prevalence of vascular calcifications.

Adipocyte-induced transdifferentiation of osteoblasts and its potential role in age-related bone loss.

Our preliminary findings have lead us to propose bone marrow adipocyte secretions as new contributors to bone loss. Indeed, using a coculture model based on human bone marrow stromal cells, we previously showed that soluble factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. In this study, microarray gene expression profiling showed profound transcriptomic changes in osteoblasts following coculture and confirmed the enrichment of the adipocyte gene signature. Double immunofluorescence microscopic analyses demonstrated the coexpression of adipogenic and osteoblastic specific markers in individual cells, providing evidence for a transdifferentiation event. At the molecular level, this conversion was associated with upregulated expression levels of reprogramming genes and a decrease in the DNA methylation level. In line with these in vitro results, preliminary immunohistochemical analysis of bone sections revealed adipogenic marker expression in osteoblasts from elderly subjects. Altogether, these data suggest that osteoblast transdifferentiation could contribute to decreased bone mass upon ageing.

Mapping the 3D orientation of nanocrystals and nanostructures in human bone: Indications of novel structural features.

Bone is built from collagen fibrils and biomineral nanoparticles. In humans, they are organized in lamellar twisting patterns on the microscale. It has been a central tenet that the biomineral nanoparticles are co-aligned with the bone nanostructure. Here, we reconstruct the three-dimensional orientation in human lamellar bone of both the nanoscale features and the biomineral crystal lattice from small-angle x-ray scattering and wide-angle x-ray scattering, respectively. While most of the investigated regions show well-aligned nanostructure and crystal structure, consistent with current bone models, we report a localized difference in orientation distribution between the nanostructure and the biomineral crystals in specific bands. Our results show a robust and systematic, but localized, variation in the alignment of the two signals, which can be interpreted as either an additional mineral fraction in bone, a preferentially aligned extrafibrillar fraction, or the result of transverse stacking of mineral particles over several fibrils.

Changes in treatment needs of hypoparathyroidism during pregnancy and lactation: A case series.

OBJECTIVE: As only sparse data are available, we aimed to investigate whether needs for activated vitamin D and calcium supplements change in women with hypoparathyroidism during pregnancy and lactation and risk of pregnancy-related complications. DESIGN: Retrospective review of medical records. PATIENTS: Twelve Danish and Canadian patients with chronic hypoparathyroidism who completed 17 pregnancies. MEASUREMENTS: Data were extracted on plasma levels of ionized calcium (P-Ca2+ ) and doses of active vitamin D and calcium supplements during pregnancy (N = 14) and breastfeeding (N = 10). Data on pregnancy complications were available from all 17 pregnancies. RESULTS: Although average doses of active vitamin D (P = .91) and calcium supplements (P = .43) did not change during pregnancies, a more than 20% increase or decrease in dose of active vitamin D was needed in more than half of the pregnancies in order to maintain normocalcemia. Five women (36%) developed hypercalcaemia by the end of pregnancy or start of lactation. Median levels of P-Ca2+ increased from 1.20 mmol/L in third trimester to 1.32 mmol/L in the post-partum period (P < .03). Accordingly, the average dose of active vitamin D was significantly reduced (P = .01) during lactation compared to 3rd trimester. One woman developed severe pre-eclampsia (6%). Further four pregnancies (24%) were complicated by polyhydramnios, dystocia and/or perinatal hypoxia. Ten pregnancies required caesarean delivery (59%) with four (24%) being performed as an emergency. CONCLUSION: In chronic hypoparathyroidism, close medical monitoring of the mother with frequent adjustments in the dose of calcium and active vitamin D is required during pregnancy and lactation in order to maintain normocalcemia. Patients should be offered close obstetric care to handle potential perinatal complications. We recommend evaluating the neonate immediately after birth and notifying the paediatrician of the risks of hypocalcaemia as well as hypercalcaemia in the neonate.

Effects of Elevated Parathyroid Hormone Levels on Muscle Health, Postural Stability and Quality of Life in Vitamin D-Insufficient Healthy Women: A Cross-Sectional Study.

Independently of plasma 25-hydroxyvitamin D (P-25(OH)D) levels, elevated parathyroid hormone (PTH) levels may exert an adverse effect on muscle health, postural stability, well-being, and quality of life. Using a cross-sectional design, we investigated 104 healthy postmenopausal women with low P-25(OH)D (< 50 nmol/l) levels, who had either secondary hyperparathyroidism (SHPT) with elevated PTH levels (> 6.9 pmol/l, n = 52) or normal PTH levels (n = 52). The average PTH value in women with SHPT was 8.5 (interquartile range 7.5-9.7) pmol/l and 5.3 (4.4-6.3) pmol/l in women with normal PTH (p < 0.001). Plasma phosphate was significantly lower in women with SHPT than in women with normal PTH (1.01 ± 0.14 vs. 1.09 ± 0.13 mmol/l; p < 0.01). In the total cohort, average level of 25(OH)D were 38 (31-45) nmol/l, with no differences between groups. SHPT was associated with impaired muscle strength as assessed by both maximum muscle strength and maximum force production at knee flexion with the knee fixed at 60° and 90° (pall < 0.05). Postural stability was impaired during semi tandem standing (p = 0.001). However, the two groups did not differ in terms of self-reported physical activity, muscle-related symptoms, quality of life, or lean muscle mass as assessed by dual-energy X-ray absorptiometry. Independently of 25(OH)D levels, mild to moderately elevated PTH levels are associated with adverse effects on muscle strength and postural stability. Why some individuals respond to vitamin D insufficiency with an elevated PTH and others do not need further elucidation, but elevated PTH itself seems to affect muscle function and postural stability.

Dental anomalies and orthodontic characteristics in patients with pseudohypoparathyroidism.

BACKGROUND: Pseudohypoparathyroidism (PHP) is a rare and inherited disease caused by mutations in the GNAS-gene or upstream of the GNAS complex locus. It is characterized by end-organ resistance to PTH, resulting in hypocalcemia and hyperphosphatemia. We aimed to investigate the dental anomalies according to tooth types and the orthodontic characteristics of patients with PHP. METHODS: Using a cross-sectional design, 29 patients (23 females) with PHP, living in Denmark, were included, and their clinical intraoral photos and radiographs were examined. RESULTS: Pulp calcification was found in 76% of the patients. Blunting of root apex was present in 55% and shortening of root in 48% of the examined patients. Blunting and shortening of roots were seen more often in premolars than in other tooth types (pboth < 0.01). Crowding of lower anterior teeth was frequently observed (36%) as well as diastema in the upper arch (25%), midline diastema (18%), and Class III malocclusion (11%). CONCLUSION: In the present study population, the teeth were frequently affected by pulp calcification and/or deviation of the root morphology. Blunting and shortening of root(s) were more often seen in premolars than in other tooth types. Class III malocclusion was relatively prevalent. It is important to pay attention to dental anomalies and occlusion in order to provide adequate care for patients with PHP.

Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial.

Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo, vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region (0.4 vs. - 0.7 g/cm3) and the femoral neck (2.1 vs. - 1.8 g/cm3) pall < 0.05. HRpQCT scans of the distal tibia showed reduced trabecular number (- 0.03 vs. 0.05 mm-1) and increased trabecular thickness (0.001 vs. - 0.005 mm), as well as an improved estimated bone strength as assessed by failure load (0.1 vs. - 0.1 kN), and stiffness (2.3 vs. - 3.1 kN/mm pall ≤ 0.01). Changes in 25(OH)D correlated significantly with changes in trabecular thickness, stiffness, and failure load. Three months of vitamin D3 supplementation improved bone strength and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but did not affect aBMD.

Health-related quality of life improves 1 year after parathyroidectomy in primary hyperparathyroidism: A prospective cohort study.

OBJECTIVE: Impaired quality of life (QoL) in primary hyperparathyroidism (PHPT) is commonly present. Patients may complain about nonspecific neurocognitive symptoms which can be difficult to quantify. Two different disease-specific questionnaires have been developed, that is, the parathyroid assessment of symptoms score (PAS) and the primary hyperparathyroidism quality of life (PHPQoL). Using these two questionnaires, we assessed relationship between QoL and biochemical indices in PHPT and effects of parathyroidectomy (PTX). DESIGN: A prospective cohort study. METHODS: Patients with PHPT diagnosed from 2015 to 2017 were asked to answer the questionnaires before and 12 months after PTX. Biochemistry was obtained on both occasions. RESULTS: A total of 104 PHPT patients answered PAS and PHPQoL questionnaires at baseline, with a median age of 64 years (73% females). PHPQoL score correlated inversely with ionized calcium and PTH at baseline (P Ë‚ 0.04). Total PAS and PHPQoL score did not differ between those with and without osteoporosis, renal calcifications and impaired renal function. Based on levels of ionized calcium, PHPQoL differed significantly between patients with mild- and moderate-severe hypercalcemia (P = 0.01). Fifty-three patients answered PAS and PHPQoL 12 months after PTX showing an improved QoL at follow-up (Pall  Ë‚ 0.02). Stratifying patients into groups based on levels of ionized calcium showed a significantly improved PHPQoL score in patients with mild (˂1.45 mmol/L) as well as moderate-severe hypercalcemia (≥1.45 mmol/L) at follow-up (Pall  Ë‚ 0.03). CONCLUSION: Quality of life improved 12 months after PTX in PHPT patients. Impaired QoL seems to be associated with the degree of hypercalcemia rather than organ manifestations attributable to PHPT.

Cardiovascular findings in patients with nonsurgical hypoparathyroidism and pseudohypoparathyroidism: A cohort study.

OBJECTIVE: As only sparse data are available on indices of cardiovascular health among patients with nonsurgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP), we aimed to compare the cardiovascular profile between these groups of patients. METHODS: A total of 56 patients with Ns-HypoPT and 30 with PHP were included and underwent a clinical examination including blood sampling and measurements of arterial stiffness, pulse wave velocity (PWV) and blood pressure (BP). Arterial stiffness and PWV were measured using AtCor SphygmoCor-XCEL (Atcor Medical Pty Ltd, Sydney, NSW, Australia). RESULTS: Patients with Ns-HypoPT had an average age of 47 ± 17 years (68% females) and PHP patients 36 ± 13 years (80% females). Over 70% in both groups were genetically screened. Groups did not differ in terms of a history of cardiovascular disease, smoking status, use of calcium and vitamin D supplements or treatment with cholesterol-lowering or antihypertensive drugs. Compared with Ns-HypoPT, PHP patients had significantly lower levels of high-density lipoproteins (HDL) cholesterol and average glucose from HbA1c (Pboth  = 0.01). PWV was significantly higher among patients with Ns-HypoPT (Pcrude  = 0.02), even after adjustment for mean arterial pressure, body mass index, age and gender (Padjusted  < 0.01). Heart rate was significantly higher in Ns-HypoPT compared with PHP (P = 0.03). Office BP and 24-hour ambulatory BP did not differ between groups (P > 0.05). CONCLUSION: Patients with Ns-HypoPT have compared with PHP a higher arterial stiffness and heart rate. This has been associated with an increased risk of cardiovascular disease. Our data suggest that resistance to PTH is present in the cardiovascular system in PHP.

The effect of vitamin D3 supplementation on markers of cardiovascular health in hyperparathyroid, vitamin D insufficient women: a randomized placebo-controlled trial.

PURPOSE: Emerging data supports an association between parathyroid hormone (PTH) and aldosterone. It has been speculated, that potential adverse cardiovascular effects of vitamin D insufficiency may partly be caused by the development of secondary hyperparathyroidism with increased activity of the renin-angiotensin-aldosterone system (RAAS). We aimed to investigate the effect of normalizing vitamin D status and/or reducing PTH levels on RAAS activity and other markers of cardiovascular health. METHODS: In a double-blinded study during wintertime, we randomized 81 healthy postmenopausal women with secondary hyperparathyroidism (PTH > 6.9 pmol/l) and 25-hydroxy-vitamin D (25(OH)D) levels < 50 nmol/l to 12 weeks of treatment with vitamin D3 70 µg/day (2800 IU/day) or identical placebo. Markers of cardiovascular health were defined as changes in the plasma RAAS, glycated hemoglobin, lipids, and lipoproteins, blood pressure, vascular stiffness, heart rate, and cardiac conductivity. RESULTS: Compared to placebo, vitamin D3 treatment significantly increased plasma levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI: 189-272%) and 58% (190-271%), respectively. Vitamin D3 treatment reduced PTH by 17% (11-23%), but did not reduce RAAS activity. Compared to placebo, vitamin D3 treatment increased plasma levels of high-density lipoproteins (HDL) by 4.6% (0.12-9.12%), but did not affect other measured indices. CONCLUSIONS: Vitamin D3 supplementation normalized vitamin D levels and reduced PTH. The supplement increased levels of HDL, but had no effects on RAAS activity or other indices of cardiovascular health.

Dental Findings in Patients With Non-surgical Hypoparathyroidism and Pseudohypoparathyroidism: A Systematic Review.

Background: Dental aberrations have been mentioned in relation to non-surgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP). However, a systematic review of dental characteristics have not been performed. The present systematic review describes the dental findings in patients with Ns-HypoPT and PHP. Methods: Studies on Ns-HypoPT and PHP reporting dental features were eligible. A systematic literature search was conducted using four bibliographic databases (Web of Science, Scopus, Pubmed, and Embase) and was limited to studies written in English. Reviews, meta-analyses and letters were excluded. Both the research and reporting of results were based on PRISMA (preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Results: Of 88 studies included, nine were cross-sectional, one was a prospective cohort study, 26 were case series, and 52 were case reports. The most frequently reported findings in patients with Ns-HypoPT were enamel opacities, enamel hypoplasia, hypodontia, and eruption disturbances. In patients with PHP, enamel hypoplasia, eruption disturbance, and deviation of the root morphology were the most frequently reported findings. Conclusion: An association between enamel hypoplasia and Ns-HypoPT and PHP is likely. The results should, however, be interpreted cautiously due to the limited number of high-quality studies. The present review confirms the need of further well-designed studies, such as large-scale studies, e.g., multicenter studies, to conclude on the reported associations between Ns-HypoPT/PHP and enamel hypoplasia.