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The pathophysiological basis for the increased incidence of cardiovascular disease in patients with chronic hypoparathyroidism is poorly understood. To evaluate associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product with the odds of developing cardiovascular events in patients with chronic hypoparathyroidism with ≥1 calcitriol prescription, we conducted a retrospective nested case-control study of patients who developed a cardiovascular event and matched controls without an event. The primary outcome was the instance of cardiovascular events. An electronic medical record database was used to identify 528 patients for the albumin-corrected serum calcium analysis and 200 patients for the serum phosphate and calcium-phosphate product analyses. Patients with ≥67% of albumin-corrected serum calcium measurements outside the study-defined 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) range had 1.9-fold higher odds of a cardiovascular event (adjusted odds ratio, 95% confidence interval 1.89, 1.10 to 3.25) compared with patients with 2/L2 (55 mg2/dL2) had 4.8-fold higher odds of a cardiovascular event (95% confidence interval 1.36 to 16.81) compared with patients with no measurements above these ranges. In adult patients with chronic hypoparathyroidism, a cardiovascular event was more likely in those with a higher proportion of albumin-corrected serum calcium measurements outside 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) or any serum phosphate and any calcium-phosphate product measurements above the normal population range.

The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy, constituting 80% to 90% of all cases. Although less common, several nonparathyroid endocrine disorders are associated with hypercalcemia. The most well described is hyperthyroidism, although the reported prevalence of hypercalcemia in hyperthyroid patients varies depending on applied method for measuring serum calcium levels. Also, adrenal insufficiency, pheochromocytoma, and vasoactive intestinal polypeptide are associated with hypercalcemia. These are differential diagnoses when assessing the hypercalcemic patient for whom common causes have been excluded. Further investigation is needed regarding hypothyroidism; acromegaly, hyperprolactinemia, gonadal dysfunction, and diabetes are not associated with hyperthyroidism.

OBJECTIVES: Vitamin D insufficiency (blood 25-hydroxyvitamin D METHODS: In this randomized, multiple crossover trial, we enrolled 30 postmenopausal women 60 to 80 y of age with vitamin D insufficiency. We measured changes in serum concentrations of vitamin D3 (D3) postprandially for 24 h in response to the intake of 500 mL of different food matrices with 200 µg D3 added compared with a control (500 mL of water). Foods included apple juice with whey protein isolate (WPI), apple juice, semi-skim milk, and water (with D3). The food matrices were provided in a randomized order with ≥10-d washout period between them. On each intervention day, blood samples were collected at 0, 2, 4, 6, 8, 10, 12 and 24 h.RESULTS: D3 with WPI in juice did not enhance area under the curve (AUC) of serum D3 compared with juice without WPI (370 nmol × 24 h/L; 95% confidence interval [CI], 321-419 versus 357 nmol × 24 h/L; 95% CI, 308-406 nmol × 24 h/L; P = 0.65). However, compared with juice, the AUC was significantly higher in response to the intake of D3 in milk (452 nmol × 24 h/L; 95% CI, 402-502 nmol × 24 h/L) and water with D3 (479 nmol × 24 h/L; 95% CI, 430-527 nmol × 24 h/L; P < 0.05). No difference was observed between milk and water (P = 0.34).CONCLUSIONS: The bioavailability of D3 was superior in milk and water compared with juice, regardless of whether WPI was added.

Hypoparathyroidism is a rare disease often resulting from neck surgery. Patients with hypoparathyroidism have hypocalcemia with low levels of parathyroid hormone (PTH) that in adults affect bone turnover and are often associated with increased bone mass. Until recently, treatment of the disease was focused on stabilizing serum calcium levels and controlling symptoms. This review summarizes how bone is affected by the condition, reflected in biochemical markers of bone turnover, bone mineral density, and histomorphometric indices and how PTH peptides [both full-length PTH(1-84) and PTH(1-34)] modulate these skeletal indices. The analysis is timely in that PTH(1-84) has recently become available to treat this disorder.

Biominerals typically have complex hierarchical structures traversing many length scales. This makes their structural characterization complicated, since it requires 3D techniques that can probe full specimens at down to nanometer-resolution, a combination that is difficult – if not impossible – to achieve simultaneously. One challenging example is bone, a mineralized tissue with a highly complex architecture that is replete with a network of cells. X-ray computed tomography techniques enable multiscale structural characterization through the combination of various equipment and emerge as promising tools for characterizing biominerals. Using bone as an example, we discuss how combining different X-ray imaging instruments allow characterizing bone structures from the nano- to the organ-scale. In particular, we compare and contrast human and rodent bone, emphasize the importance of the osteocyte lacuno-canalicular network in bone, and finally illustrate how combining synchrotron X-ray imaging with laboratory instrumentation for computed tomography is especially helpful for multiscale characterization of biominerals.

CONTEXT: Ketone bodies, in particular 3-hydroxybutyrate (3OHB), are known to possess important energetic and signaling capacities. There is a growing block of evidence, that ketogenic dieting (KD), fasting, and sodium glucose transporter 2 inhibitor (SGLT2i) treatment are associated with hyperparathyroidism and negative bone health.OBJECTIVE: We aimed to study the effect of exogenous 3OHB administration on bone metabolism, specifically the effect on parathyroid hormone (PTH) and calcium/phosphate homeostasis.DESIGN: A randomized, controlled, cross over study with two arms: i) saline infusion and ii) 3OHB infusion.SETTING: The study was conducted at Aarhus University Hospital.PARTICIPANTS: We examined eight healthy human subjects aged 50-70 years.INTERVENTION: Continuous intravenous DL-3OHB-NaCl infusion or 0.9% NaCl was administered for 390 minutes.MAIN OUTCOME MEASURES: The study was designed to test the impact of 3OHB on PTH, calcium-phosphate, C-terminal Telopeptide (CTX), and Procollagen I N-terminal Propeptide (PINP). The study was a post hoc study.RESULTS: The PTH concentration increased by 25% with a concomitant drop in phosphate of 30% in the 3OHB group. 3OHB infusion increased concentrations of CTX by 5%, without changes in PINP and albumin corrected calcium concentrations.CONCLUSION: In conclusion, 3OHB administration increases PTH concentration and markers of bone resorption. These findings suggest a possible negative effect on bone health, which needs to be determined in future studies.

Udgivelsesdato: 2008-Nov BACKGROUND: Little is known on fracture risk in young women using oral contraceptives. STUDY DESIGN: Case-control study (64,548 cases, 193,641 controls). RESULTS: Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day - i.e., intermittent use). Neither 20 nor >or=30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to >or=30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups. CONCLUSIONS: In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.

L’hyperparathyroidie primitive (PHPT) est une maladie frequente, curable (chirurgie), compliquee d’atteintes renales et osseuses. L’hypercalcemie familiale benigne (FHH) est une maladie genetique rare, non curable dont la presentation biologique est proche de celle de la PHPT : une hypercalcemie associee a une concentration d’hormone parathyroidienne (PTH) inadaptee. La mesure de l’excretion fractionnelle de calcium (FE Ca ) est recommandee pour distinguer ces 2 affections. Methodes D’une premiere cohorte, 146 adultes (63 avec FHH genetiquement prouvee, 83 avec PHPT chirurgicalement prouvee) ont ete etudies. Tous avaient une hypercalcemie ([calcium ionise] a jeun ≥ 1,32 mM) et une PTH normale. Les donnees disponibles ont ete comparees en analyse multivariee afin de developper une equation de risque (Pro-FHH) pour distinguer les patients avec FHH de ceux avec PHPT. Apres une validation interne ( boot-strap ), une cohorte independante, incluant 38 adultes avec FHH et 55 avec PHPT, a permis de tester la validation externe. Resultats Les patients avec FHH et ceux avec PHPT avaient des valeurs de calcemie, PTH, osteocalcine et FE Ca differentes. Pro-FHH a ete developpee grâce a ces 4 valeurs. L’aire sous la courbe ROC etait plus elevee pour Pro-FHH que pour FE Ca (0,969 vs. 0,873, p Ca classait de facon erronee 24 patients, pro-FHH les classait correctement. Ces resultats sont confirmes dans une cohorte independante. Discussion Pro-FHH a une meilleure capacite a discriminer la FHH et la PHPT que FE Ca. Une evaluation prospective de cet outil simple est necessaire.

Hypoparathyroidism is characterized by hypocalcemia with inappropriately low parathyroid hormone (PTH) levels. Bone turnover is abnormally low and bone mineral density (BMD) is typically increased. Plasma calcium levels can be normalized by treatment with calcium supplements and vitamin D analogs, but bone turnover remains low and patients complain of a reduced quality of life (QoL). During recent years, a number of studies have shown that PTH replacement therapy (PTH-RT) may maintain calcium levels within the normal range, while the need for calcium and vitamin D supplements is reduced. In the initial response to subcutaneous PTH injections once or twice daily, bone turnover is overstimulated. BMD increases in cancellous bone, but decreases in cortical bone due to an increased porosity. Microcomputed tomography scans and histomorphometric studies on bone biopsies have shown changes similar to the well-known bone anabolic effects of PTH treatment in osteoporosis rather than a normalization of bone remodeling balancing the anabolic and catabolic effects of PTH. Most recently, continuous PTH delivery by pump was shown to increase the levels of bone markers into the normal range (without overstimulation of bone turnover) and with a normalization of renal calcium excretion. As PTH has a short plasma half-life, these findings indicate that exposure to PTH once or twice daily is not sufficient to reestablish a calcium homeostasis and bone metabolism that resembles normal physiology. Further studies should assess the effects of continuous PTH exposure by pump delivery (or multiple daily injections) on BMD and bone histology, as well as the effects of PTH-RT on indices of QoL.