Mechanical loading and intermittent parathyroid (iPTH) treatment are both osteoanabolic stimuli and are regulated by partially overlapping cellular signaling pathways. iPTH has been shown clinically to be effective in increasing bone mass and reducing fracture risk. Likewise, mechanical stimulation can significantly enhance bone apposition and prevent bone loss, but its clinical effects on fracture susceptibility are less certain. Many of the osteogenic effects of iPTH are localized to biomechanically suboptimal bone surfaces, whereas mechanical loading directs new bone formation to high-stress areas and not to strain-neutral areas. These differences in localization in new tissue, resulting from load-induced versus iPTH-induced bone accumulation, should affect the relation between bone mass and bone strength, or "tissue economy." We investigated the changes in bone mass and strength induced by 6 weeks of mechanical loading and compared them to changes induced by 6 weeks of iPTH treatment. Loading and iPTH both increased ulnar bone accrual, as measured by bone mineral density and content, and fluorochrome-derived bone formation. iPTH induced a significantly greater increase in bone mass than loading, but ulnar bone strength was increased approximately the same amount by both treatments. Mechanical loading during growth can spatially optimize new bone formation to improve structural integrity with a minimal increase in mass, thereby increasing tissue economy, i.e., the amount of strength returned per unit bone mass added. Furthermore, exercise studies in which only small changes in bone mass are detected might be more beneficial to bone health and fracture resistance than has commonly been presumed.

Aluminium accumulation in serum and tissues is a well-known complication in patients with chronic renal failure, and retention of the element in bone has been implicated in the pathogenesis of the so-called aluminium-related bone disease (ARBD). Regular serum aluminium monitoring remains mandatory to detect patients and centres at risk for aluminium intoxication. Early recognition of ARBD however requires a desferrioxamine (DFO) test in combination with a serum iPTH measurement. Definite diagnosis of ARBD is made by histological examination of a bone biopsy. Once ARBD has been identified DFO treatment should be initiated and all potential sources of aluminium exposure eliminated. In order to minimize the risk for DFO-related cerebral, auditory and visual side-effects, and siderophore-mediated opportunistic infections the chelator should be used at low doses (5 mg/kg) and administered widely spaced (once weekly) following well-defined strategies of administration.

Data suggest a link of aortic stenosis (AS) with calcium and bone metabolism. To further investigate this, the following parameters were analyzed in 38 patients with severe AS and in 38 age- and gender-matched controls, without obstructive coronary artery disease and with preserved renal function: calcium, phosphate, 1,25(OH(2))-vitamin D(3), intact parathyroid hormone (iPTH), and osteoprotegerin. Patients with AS had significantly higher serum levels of calcium (2.63 +/- 0.28 vs 2.48 +/- 0.23 mmol/L, p <0.01) and phosphate (1.56 +/- 0.33 vs 1.38 +/- 0.26 mmol/L, p <0.01) and increased calcium-phosphorus products (4.16 +/- 1.13 vs 3.44 +/- 0.89 mmol/L(2), p = 0.003). Notably, the iPTH concentration in the AS group was lower, and significantly more patients in the AS group had levels less than the study median of 60 ng/L. Osteoprotegerin was elevated in patients with AS, confirming reports in other populations (9.94 +/- 5.96 vs 6.73 +/- 4.28 pmol/L, p = 0.009). The relations of several parameters to iPTH were also altered (AS vs controls): calcium and iPTH, 0.071 +/- 0.034 versus 0.046 +/- 0.023, p <0.0001; phosphate and iPTH, 0.042 +/- 0.020 versus 0.025 +/- 0.013, p <0.0001; vitamin D and iPTH, 0.99 +/- 0.61 versus 0.63 +/- 0.46, p = 0.006; and osteoprotegerin and iPTH, 0.24 +/- 0.15 versus 0.12 +/- 0.09, p <0.0001. In conclusion, these data support a hypothesis connecting (severe) AS to altered calcium and bone homeostasis.

BACKGROUND

Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival.

METHODS

We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (Ca(Alb)), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011.

RESULTS

Across all MBD markers (Phos, Ca(Alb), iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up.

CONCLUSIONS

There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population.

OBJECTIVE

Chronic renal failure (CRF) is often associated with bone disorders including chronic kidney disease-mineral and bone disorder (CKD-MBD). Parathyroid hormone (PTH) has a relationship to bone remodeling, and so this study was undertaken to evaluate changes in bone remodeling markers after parathyroidectomy (PTX).

METHODS

Twelve adult patients, mean age 43.4 +/- 12.7 years, of both genders, were evaluated, prior to and six months after PTX. Analysis of biochemical markers of bone metabolism, such as total and ionized calcium, phosphorus, 25(OH)D(3), total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), intact PTH, osteoprotegerin (OPG), and tartrate-resistant acid phosphatase isoform 5b (TRAP), were measured.

RESULTS

No changes were observed after PTX in the serum total and ionized calcium, TAP, BAP, and 25(OH)D(3). After surgery there was a significant decrease in serum phosphorus, iPTH, and TRAP (P < 0.001). No significant change was observed in OPG; however there was a positive correlation between OPG and 25(OH)D(3) before and after surgery (r = 0.774, P = 0.014; and r = 0.706, P = 0.01, respectively). The percentage of patients with vitamin D deficiency decreased from 16.7% to 8.3%, while those with sufficient levels increased from 41.7% to 58.3%.

CONCLUSIONS

The small number of patients in the study notwithstanding, the present study is unique because it provides information on bone metabolism and vitamin D status six months after PTX. The removal of parathyroid glands significantly decreased bone resorption and indicated a tendency of 25(OH)D(3) concentration to increase. However, the precise role of OPG and BAP in the improvement in bone remodeling in patients with CKD-MBD requires further study.

In a cross-sectional, age-matched study, vitamin D status and skeletal status were compared between 26 Pakistani premenopausal women living in Oslo and 24 Norwegian women. The serum calcidiol concentration was significantly lower in Pakistani women (mean and 95% confidence interval (CI) 22 (16-27) nmol l-1 vs. 65 (55-74) nmol l-1, p < 0.001) and serum iPTH significantly higher (5.4 (4.1-6.8) pmol l-l vs. 3.4 (3.0-3.7) pmol l-1, p<0.05). No differences concerning bone mineral density (BMD) measured by DXA in the lumbar spine, femoral neck and total body or ultrasound parameters of the calcaneus were found between the Pakistani and Norwegian women. The Pakistani women were advised to take vitamin D supplementation, but after 1 year no significant changes were found in serum calcidiol or serum iPTH in 17 Pakistani women. Premenopausal Pakistani women living in Oslo, Norway seem to have increased risk of developing vitamin D deficiency with secondary hyperparathyroidism, but there is no evidence that their skeletal strength differs from that of Norwegian women. Advice on vitamin D supplementation did not result in a normalization of the vitamin D deficiency within 1 year of follow-up.

The present study was undertaken to evaluate the acute effect of 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) on serum Ca, P and immunoreactive parathyroid (iPTH) and urinary Ca, P. and cyclic AMP. In 8 normal subjects, samples were collected over intervals of 30 to 60 min during a control day and on a treatment day following oral ingestion of 1,25(OH)2D3, 2.7 microgram. For the entire group there were no significant changes in serum Ca. P, iPTH or urinary P. Urinary Ca increased significantly 7 h after administration of 1,25(OH)2D3, and urinary cAMP decreased at 12 h. In 4 patients (group A). showing an increase in serum Ca by 0;2 to 0.4 mg/dl, serum iPTH decreased in 3, and the decrease in urinary cAMP appeared sooner. Among 4 patients showing no change in serum Ca after 1,25(HO)2D3 (group B), 3 showed an increase in iPTH. These data document the early onset of action of 1,25(OH)2D3 following its administration to normal man; increments in urinary Ca provide the most sensitive index of its action. The data provide no support for the view that 1,25(OH)2D3 exerts any direct inhibitory effect on the secretion of parathyroid hormone.

OBJECTIVE

To determine the dose-response relationship between 25-hydroxyvitamin D (25(OH)D) and supplemental vitamin D3 in elderly nursing home residents.

METHODS

Randomized double-blind investigation.

METHODS

Nursing home.

METHODS

Of 81 women (n=51) and men (n=30) (mean age 87.4±8) enrolled, 72 completed the study.

METHODS

Sixteen weeks of oral vitamin D3 at 800, 2,000, or 4,000 IU/d or 50,000 IU/wk.

METHODS

The main outcome was 25(OH)D concentrations (tandem mass spectrometry) after 16 weeks. Free 25(OH)D and intact parathyroid hormone (iPTH) were also analyzed. Safety monitoring of calcium and estimated glomerular filtration rate was performed, and adherence and clinical status were measured.

RESULTS

25(OH)D concentrations increased with dose (P<.001) and were higher with 50,000 IU/wk (P<.001) than other doses and with 4,000 IU/d than 800 or 2,000 IU/d, but 800 IU and 2,000 IU/d did not differ. One subject receiving 800 IU/d had concentrations less than 20 ng/mL. All subjects receiving more than 2000 IU/d had concentrations of 20 ng/mL and greater. Free 25(OH)D concentrations rose with total 25(OH) vitamin D. Total and free 25(OH)D were related to calcium concentrations; only free 25(OH)D was related to iPTH.

CONCLUSIONS

25(OH)D increased linearly with 800 to 4,000 IU/d and 50,000 IU/wk of vitamin D3, without a ceiling effect. Data suggest that some elderly adults will require more than 800 IU/d of vitamin D3 to ensure adequate vitamin D levels. Changes in 25(OH)D with vitamin D3 were related to starting concentrations (greatest with the lowest concentrations and unchanged with 800 and 2,000 IU/d if 20-40 ng/mL). Relationships between serum calcium and iPTH and free 25(OH)D suggest the potential for free 25(OH)D in defining optimal 25(OH)D concentrations.

OBJECTIVE

To study if vitamin D fortification of milk products started in February 2003 has improved vitamin D status of young Finnish men, which has been poor before.

METHODS

A longitudinal study of one cohort.

METHODS

Helsinki University Central Hospital.

METHODS

Sixty-five healthy men, studied for the first time in January 2001, were re-examined in January 2004. They were aged 18-21 years in 2001.

METHODS

Blood was sampled for determination of serum 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH). 25-OHD was measured by both radioimmunoassay (RIA) and high-pressure liquid chromatography (HPLC). Consumption of milk, sour milk and fish and use of vitamin D supplements were assessed using a questionnaire.

RESULTS

In January 2004, vitamin D fortification had raised serum 25-OHD level, with the mean of individual percent changes being 20.4% measured with RIA (P=0.0015). The correlation between the RIA and HPLC methods was high (r=0.85). Nineteen men (29.2%) had vitamin D deficiency (25-OHD<or=20 nmol/l) and 48 men (73.8%) had hypovitaminosis D (25-OHD<or=37.5 nmol/l). Serum 25-OHD and <em>iPTH</em> levels correlated inversely (r=-0.30; P=0.017). Serum 25-OHD levels were 52.0% higher for 13 vitamin D supplement users than for 51 non-users (P=0.0001). After exclusion of supplement users, an association between 25-OHD level and consumption of milk products was found (P=0.011), with the median vitamin D level being 6.5 nmol/l higher for those consuming four glasses of milk products or more daily than for those consuming one or less. Likewise, the higher the milk consumption, the higher the difference in 25-OHD between years 2004 and 2001 (P=0.0025).

CONCLUSIONS

Vitamin D fortification of milk products slightly but insufficiently improved the poor vitamin D status of young Finnish men during winter. Further supplementation is warranted in order to normalize vitamin D levels and to support achievement of maximum peak bone mass.

BACKGROUND

Supported by Paulo Foundation, Juho Vainio Foundation, Emil Aaltonen Foundation and Research Funding from Helsinki University Central Hospital (Erityisvaltionosuus).

The parathyroids from ten consecutive cases of chronic renal failure coming to operation in a period of seven years were studied by light and electron microscopy. The clinical and biochemical data as well as the levels of immunoreactive parathormone (iPTH) were reviewed. For the sake of comparison adenomata from two cases of primary hyperparathyroidism were studied. In the cases of chronic ;renal failure there were six cases of tertiary hyperparathyroidism with adenoma formation, surrounded by dense fibrous tissue and compression of adjacent parathyroid cell amidst a background of hyperplasia. Two cases showed secondary parathyroid hyperplasia and the remaining two cases were adenomata which clinically affected only one gland. Neither the biochemical data nor levels of iPTH allowed the cases with secondary hyperplasia to be separated from those with tertiary hyperparathyroidism. Similarly electron microscopy showed no distinct differences between these two groups of adenomata from cases of primary hyperparathyroidism. The diagnosis of tertiary hyperparathyroidism is made on a combination of clinical, biochemical and histological features, the histological features being most important. It is concluded that tertiary hyperparathyroidism is part of a histological spectrum in response to chronic renal failure and autonomous glands are related to the mass of parathyroid tissue present.

OBJECTIVE

High prevalence of vitamin D insufficiency/deficiency has been reported in populations of different countries. The aim of this cross-sectional study was to determine the prevalence and association of vitamin D status with components of metabolic syndrome.

METHODS

Lipid profile indices, anthropometric indices [body mass index and waist circumference (WC)], insulin resistance index (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), C-reactive protein, intact parathyroid hormone (iPTH), and serum 25-hydroxyvitamin D [25(OH)D] concentration were evaluated in 297 healthy schoolchildren aged 7-11 years. Multivariate linear regression was used to determine independent predictors associated with low serum 25(OH)D concentrations.

RESULTS

The mean serum 25(OH)D concentration was 14.12±8.20 ng/mL (35.3±20.5 nmol/L); 96% of children had low serum 25(OH)D levels, 31.0% were deficient, and 65.0% had insufficient levels of 25(OH)D. Vitamin D deficiency was higher in girls (χ²=13.66; p=0.00); 25(OH)D level was negatively associated with WC, HOMA-IR, SBP, DBP, and iPTH. In the multivariate model, WC, DBP, and HOMA-IR were significant independent predictor of low 25(OH)D concentrations.

CONCLUSIONS

The prevalence of low vitamin D level in the studied healthy children was high and it is correlated with some components of metabolic syndrome. Outdoor activity for optimum sun exposure and additional studies are needed to evaluate the underlying metabolic syndrome components and hypovitaminosis D complications.

Osteoporosis in men is a significant health problem, and factors associated with bone mass are being investigated. Although osteoporosis is a typical feature of hypogonadism, the influence of testosterone levels and other hormonal factors on bone mass of eugonadal males is unknown. Our aim was to identify several anthropometric and hormonal predictors that could be responsible for the variability in bone mineral density (BMD) in healthy men. One hundred elderly men (age 68 +/- 7 years) were investigated in this cross-sectional study. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral sites (femoral neck, Ward's triangle, trochanter, intertrochanter and total femur). Anthropometric measures were obtained including: weight, height, body mass index (BMI), waist-hip ratio and testicular volume. Hormonal data measures were total, free and bioavailable testosterone, dihidrotestosterone, estradiol, sex hormone binding globulin (SHBG), insulin-like growth factor I (IGF-I), intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). One subject was excluded because primary hypogonadism was found. SHBG levels were increased in 53.5% of men, and 8% showed a mild increase in iPTH levels. Twenty-eight subjects had densitometric criteria of osteoporosis (T-score < or = -2.5). All BMD sites were positively correlated with body weight (r = 0.29-0.48, p < 0.001) and BMI (r = 0.24-0.47, p < 0.001). A negative correlation between SHBG levels and intertrochanter (IT) and total femur (TL) BMD was found (r = -0.24 and r = -0.22, p < 0.05). After adjusting for age and BMI, SHBG and IGF-I levels were negatively correlated (r = -0.33, p < 0.001). In multiple linear regression analysis independent predictors of bone mass were body weight, SHBG and iPTH levels. The best predictive model accounted for 24-40% of the observed variability of BMD. However, most of the BMD variability was explained by body weight. In conclusion, in our study body weight, SHBG and iPTH levels were predictors of BMD in healthy elderly men.

Previous studies have suggested a role for adrenergic stimuli in the regulation of PTH secretion. In the present studies, we evaluated the effect of endogenous catecholamine stimulation (by treadmill exercise) on serum calcium (Ca) and immunoreactive PTH (iPTH) in six healthy volunteers. Blood was collected for serum total Ca, ionized Ca, iPTH, cAMP, epinephrine, and norepinephrine before, during, and after exercise. As expected, plasma cAMP and catecholamine levels increased significantly during the exercise. In addition, there was an increase in serum total and plasma ionized Ca. However, serum iPTH levels did not change significantly at any of the times tested during and after exercise. The lack of change in serum PTH despite an increase in plasma catecholamines may be explained by 1) an increase in plasma ionized Ca by a separate mechanism (such as metabolic acidosis), which blocked an increase in serum iPTH, or 2) insufficient increase in plasma catecholamines to stimulate PTH secretion.

BACKGROUND

The cushioning function of the arterial system is altered in patients with end-stage renal failure. The role of hyperparathyroidism for the altered vessel wall properties of large arteries not known.

METHODS

To exclude the confounding effects of fluid volume changes and hypercirculation as well as uremic toxicity on vessel wall properties from those of hyperparathyroidism, the present study was conducted in 54 normotensive renal transplant recipients with good graft function, three to six months after transplantation. The vessel wall properties of the common carotid artery were investigated in 32 of them, who had increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter, SEM), and compared to those of 22 control recipients of same age with normal plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by Doppler analysis of the vessel wall movements, blood pressure was determined by sphygmomanometry.

RESULTS

Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in patients with normal plasma iPTH levels (NS). There was no difference in enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal transplant recipients with hyperparathyroidism as compared with the control patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28 microns, P < 0.05) and distensibility coefficient of the common carotid artery (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared with the control patients. Multiple regression analysis showed that the distensibility coefficient of the common carotid artery was negatively correlated with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH levels (P < 0.05). The effects of plasma iPTH levels were not related to serum calcium concentrations or to differences in the enddiastolic diameter of the common carotid artery.

CONCLUSIONS

The data suggest that secondary hyperparathyroidism can affect the cushioning function of larger arteries in patients with end-stage renal failure independently of high blood pressure.

Tc-99m MIBI has been widely used to evaluate hyperparathyroidism based on increased tracer uptake in hyperfunctioning parathyroid tissue. The functional status measurement of parathyroid glands with intact parathyroid hormone (iPTH) levels is also one of the most important diagnostic studies in this disorder. The aim of the current study was to assess the relation between MIBI imaging and iPTH levels. The authors retrospectively reviewed the records of patients with hyperparathyroidism who were referred to their department for Tc-99m MIBI scintigraphy. Sixty-five patients (24 primary and 41 secondary hyperparathyroidism) were included. The iPTH levels ranged from 66.06 to 2,836 pg/ml (normal, 10 to 55 pg/ml). Forty-two patients were MIBI positive and 23 were negative. The iPTH level in the MIBI-positive group was significantly greater than in the negative group in the primary (548 +/- 478 versus 124 +/- 45; = 0.002), secondary (1,155 +/- 692 versus 501 +/- 352; < 0.001), and overall (909 +/- 678 versus 386 +/- 341; < 0.001) groups. For the primary hyperparathyroidism group, 17 of the 24 patients were MIBI positive (71%). When iPTH levels exceeded 200 pg/ml (100%), the diagnostic sensitivity reached 100%. For the secondary hyperparathyroidism group, 25 of 41 patients (61%) were MIBI positive; 24 of 38 patients (63%) had an iPTH level greater than 200 pg/ml, 21 of 27 patients (78%) had an iPTH level greater than 500 pg/ml, and 11 of 12 patients (92%) had an iPTH value greater than 1,000 pg/ml. Tc-99m MIBI parathyroid scintigraphy showed a good correlation with iPTH level for both primary and secondary hyperparathyroidism. Visualization of hyperfunctioning parathyroid glands on Tc-99m MIBI parathyroid scintigraphy was more likely with a higher serum iPTH level in a dose-dependent manner.

OBJECTIVE

Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population.

METHODS

We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH)>> 120 pg/mL) who initiated cinacalcet in the clinical practice.

RESULTS

We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P < 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P < 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy.

CONCLUSIONS

In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good.

BACKGROUND

Hypocalcemia, the most common complication of thyroidectomy, is a transient condition in up to 27% of patients and a permanent condition approximately 1% of patients. The aim of this prospective study was to evaluate reliability of postoperative intact parathyroid hormone (iPTH) assessment for predicting clinically relevant postthyroidectomy hypocalcemia for a safe early discharge of patients with no overtreatment.

METHODS

Seventy-five consecutive patients (age 51 ± 13 years [mean ± SD]) undergoing total or completion thyroidectomy with no concomitant parathyroid diseases or renal failure were included in the present study. Serum iPTH level was determined before and 2 hours after thyroidectomy. Serum calcium concentration was determined 1 day before and 2 days postoperatively.

RESULTS

The occurrence of postoperative hypocalcemia was correlated both with the absolute and relative iPTH decrease, determined as a ratio of the preoperative value (P < .0001). There was a greater difference in relative decrease in iPTH between patients remaining normocalcemic and those with hypocalcemia present on the second postoperative day. Hypocalcemic patients on the second postoperative day had a 62% relative decrease in iPTH 2 hours after thyroidectomy.

CONCLUSIONS

The relative decrease in serum iPTH was greater in patients with hypocalcemia arising on the second postoperative day rather than in patients who remained normocalcemic. The relative decrease in iPTH determined 2 hours after total thyroidectomy together with the serum calcium concentration 24 hours after thyroidectomy proved to be useful predictors of sustained hypocalcemia and might change the clinical management of patients after thyroid surgery to support a longer hospitalization in these selected patients.

A case of congenital rickets of nutritional origin is described in a light-for-date premature infant (gestational age 34 weeks, birthweight 1 100 g). X-rays of the long bones showed spread, frayed and cupped metaphyses at birth and at the age of 16 days. Serum calcium was 8.2 mg/100 ml, phosphorus 3.4 mg/100 ml and alkaline phosphatase (A.P):323 IU/ml (N less than or equal to 200) at the age of 3 days. Very high level of serum immunoreactive parathroid hormone (iPTH) was found at the age of 16 days=295 micronlEq/ml (N less than or equal to 50). Evidence of maternal vitamin D deficiency was demostrated by low plasma 25-hydroxycholecalciferol (25-OH-CC):1.0 ng/ml (N:13.2+/-4.2) soon after delivery; it was found to be normal (10.2 ng/ml) six months later. Ca infusion (15 mg/kg/3 h) resulted in a marked fall of serum iPTH (280 to 84 micronlEq/ml). Administration of vitamin D2 (2400 IU/day for 10 days) induced some healing of the metaphyses; A. P. remained elevated (400 IU/ml); plasma 25-OH-CC was normal 10.2 ng/ml and serum iPTH was 115 micronlEq/ml. When 25-OH-CC was given orally for ten days (15 microng/day), plasma 25-OH-CC rose to 64.5 ng/ml with a minor change of serum iPTH (94 micronlEq/ml); X-rays of the bones showed osteoporosis. These results suggest a reduced convertion of 25-OH-CC into 1-25-(OH)2-CC.

We report a randomized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate (alendronate), infused over 1 h, in 15 patients with Paget's disease of bone. Alendronate, 10 mg/day for 5 days, suppressed urinary hydroxyproline to 44.9 +/- 4.8% and serum alkaline phosphatase to 74.6 +/- 5.4% of their pretreatment values within 1 month of the start of treatment. Within 5 months of the start of treatment serum alkaline phosphatase fell to 47.9 +/- 6.3% of pretreatment values. These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values. A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions, and this was associated with a decrease in the total and differential white cell count. No adverse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function. This regimen may simplify the management of patients with Paget's disease of bone.

OBJECTIVE

The mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1-34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappaB ligand (RANKL) in women with established osteoporosis.

METHODS

Twenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7+/-1.6 years) received daily injections of 20 microg TPTD for 12 months.

METHODS

Serum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment.

RESULTS

Serum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P<0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels.

CONCLUSIONS

TPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD.

BACKGROUND

The available evidence indicates a progressive increase in the incidence and severity of the deficiency of certain vitamins and related clinical conditions (i.e., metabolic bone disease). Because of the potential role of fat-soluble vitamins and carotenoids in bone metabolism, our aim was to assess the time-course changes of fat-soluble vitamins and serum markers of bone metabolism in candidates for obesity surgery and following two bariatric procedures.

METHODS

Sixty-five candidates for bariatric surgery and 150 serum samples after obesity surgery (i.e., Roux-en-Y gastric bypass, n = 85; biliopancreatic diversion, n = 65) were consecutively analyzed over a period of more than 2 years. Retinol, α- and γ-tocopherol, 25-OH-vitamin D3, β-cryptoxanthin, and β-carotene were analyzed by high-performance liquid chromatography. Calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), osteocalcin, beta-crosslaps, and N-terminal peptide of procollagen I (P1NP) were determined using commercial kits.

RESULTS

Retinol, β-cryptoxanthin, β-carotene, and α- and γ-tocopherol levels were significantly lower in post-surgery samples while osteocalcin, b-crosslaps, and P1NP were significantly increased. Along the time and regardless of the surgical procedure, P1NP, b-crosslaps, and osteocalcin increased during the first 12-24 months but declined afterward. 25-OH-vitamin D increased during the first 12 months and tended to decrease afterward while iPTH remained constant or decreased but increased after 1 year in both groups. Vitamin A remained constant but α- and γ-tocopherol, β-cryptoxanthin, and β-carotene decreased in both groups.

CONCLUSIONS

In addition to the nutritional assessment, regular monitoring of bone markers seems necessary in these patients and the early introduction of preventive strategies (i.e., the use of antiresorptive agents) should be evaluated.

OBJECTIVE

A significant proportion of the older population may exhibit vitamin D insufficiency. We sought to establish the proportion of 25-hydroxyvitamin D (25OHD) insufficient individuals in an older female cohort presenting for acute medical admission and how they responded to supplementation.

METHODS

A prospective cohort study.

METHODS

Hospital admissions followed up as a population-based study.

METHODS

A total of 114 consecutive female acute medical admissions aged over 65 years from November 2003 to January 2004 were enrolled. All admissions with hypercalcaemia, metabolic bone disease (other than osteoporosis/osteomalacia) and creatinine>> 150 micromol/l were excluded.

METHODS

iPTH, calcium and 25OHD levels were measured in each patient. Of the total, 22 were already receiving calcium and vitamin D supplementation at enrolment. The remaining 92 were commenced on 800 IU of vitamin D and 1 g calcium, and levels were reassessed after supplementation for 3 months.

RESULTS

25-Hydroxyvitamin D insufficiency, as defined by a 25OHD concentration of < 50 nmol/l, was present in 86 (75.4%) patients at initial assessment (mean 35.8 nmol/l, s.d. 23.3). Secondary hyperparathyroidism was present in only 36.7% of those with 25OHD deficiency at baseline. Of the total, 51 (44.7%) patients presented for follow-up. 25-Hydroxyvitamin D concentration increased in this group from 42.1 nmol/l (s.d. 26.6) to 59.5 nmol/l (s.d. 27.4) after supplementation, P < 0.001, but 18(35.3%) still remained deficient. There was no significant change in iPTH or calcium following supplementation. Assessment of compliance revealed 6 (11.7%) admitted to partial or non-compliance.

CONCLUSIONS

Insufficiency of 25OHD was very common in this cohort. Despite calcium and vitamin D supplementation, 25OHD concentrations failed to reach normality in a significant proportion. Maintaining vitamin D and calcium intake at the level of current recommended doses may not be sufficient to ensure adequate 25OHD stores.

BACKGROUND

Diets high in either dairy or calcium during moderate weight reduction both prevent loss of bone mineral density (BMD) and suppress bone turnover. The purpose of this study was to determine whether recommended dairy and calcium intakes during weight maintenance favorably affect total body BMD (TBBMD) and bone mineral content (TBBMC) in obese adults.

METHODS

Obese men (n=49) and women (n=64), aged 40.8+/-0.6 years, underwent 12 weeks of moderate energy restriction (approximately 1200 kcal/day) followed by 24 weeks on either a low or recommended dairy weight maintenance diet. The TBBMC and TBBMD values were measured using dual energy X-ray absorptiometry at baseline, 12, 24 and 36 weeks. Concentrations of calcium, intact parathyroid hormone (iPTH), 25OH and 1,25 (OH)(2) vitamin D in plasma were also measured. Data were analyzed using a two-factor repeated measures analysis of variance.

RESULTS

After weight loss, women exhibited a small, but statistically significant, increase in TBBMC (1.17+/-0.57%), whereas TBBMD increased in the men (1.34+/-0.28%). The iPTH concentration decreased significantly in all subjects. Despite significantly greater intakes of calcium, vitamin D and protein compared with the recommended dairy diet, there were no treatment-related differences in outcome variables after 24 weeks of weight maintenance. The TBBMC remained unchanged in women during weight stabilization; both TBBMC and TBBMD decreased in men (-1.59+/-0.51% and -0.70+/-0.25%, respectively).

CONCLUSIONS

In summary, results of this study do not provide convincing evidence that moderate weight loss through energy restriction and mild exercise reduces TBBMC in obese men and women. Similarly, a weight-maintenance diet providing the recommended daily servings of dairy does not seem to affect changes in BMC after weight loss.

A 13-year-old boy with primary hyperoxaluria and a successful renal allograft developed symptomatic bone disease, hypercalcemia, and hypercalciuria. Transiliac bone biopsy revealed calcium oxalate crystals in the marrow within mononuclear phagocytes and multinucleated giant cells. Deep resorption bays were seen adjacent to these crystal-cell aggregates. Serum 1,25-(OH)2-vitamin D (calcitriol) and iPTH concentrations were low or normal. We suggest that hypercalcemia results from macrophage-mediated bone resorption initiated by Ca oxalate crystal deposition.