Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women.

PURPOSE: This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women. METHODS: Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D3, 5 µg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined. RESULTS: Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes. CONCLUSIONS: Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 µg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.

Effects of PTH (1-84) on bone quality in a validated model of osteoporosis due to androgenic deprivation.

AIM: The purpose of this study was to evaluate the effect of parathyroid hormone (PTH) (1-84) in a model of male osteoporosis induced by orchidectomy in rats. METHODS: Six-month-old Wistar rats were used as follows: SHAM (simulated orchidectomy), orchidectomized (ORX), ORX + PTH1 (ORX and treated with 10 µg/Kg/d of PTH 1-84) and ORX + PTH2 (ORX and treated with 50 µg/Kg/d of PTH 1-84) over 3 months, with treatment beginning three months after orchidectomy. RESULTS: Orchidectomy resulted in a decreased of femoral and lumbar bone mineral density (BMD), a worsening of trabecular and cortical microarchitecture and a decrease in biomechanical properties. Both doses of PTH (1-84) partially (low dose) or totally (high dose) restored the ORX-induced changes. Serum C-telopeptide of type I collagen/5b isoenzyme of tartrate-resistant acid phosphatase (CTX/TRAP) resorption index increased after orchidectomy. Osteocalcin (bone Gla protein; BGP) levels were not affected by orchidectomy. PTH (1-84) treatment did not produce any changes in the levels of CTX/TRAP with respect to the ORX group. BGP levels increased with PTH treatment. CONCLUSION: PTH (1-84) is able to restore the adverse effects of orchidectomy on bone as measured by BMD, microstructural and biomechanical properties and bone remodeling markers.

Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema.

Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia. We report the case of an 83-year-old woman with hyperphosphatemia and hypocalcemia resulting from phosphate-containing enemas. PTH and calcitriol increased in response to hypocalcemia, and FGF23 increased in response to hyperphosphatemia. Unexpectedly, peak FGF23 did not coincide with peak serum phosphate. Rather, peak FG23 was observed only after severe hypocalcemia was partially corrected with exogenous calcium administration, even though serum phosphate had been already decreasing for 32 h. Correction of severe hypocalcemia was thus associated with peak FGF23 values and with a precipitous decrease in PTH. Peak FGF23 was followed by an accelerated decrease in serum phosphate and significant phosphaturia. This clinical report is consistent with experimental data in rats showing a blunted FGF23 response to high phosphate in the presence of severe hypocalcemia. Thus, complementary experimental and clinical data suggest that partial correction of severe hypocalcemia is required for optimal FGF23-mediated phosphaturia, which takes place despite correction of PTH levels. We believe this the first human report suggesting blunting of the FGF23 response to high phosphate by severe hypocalcemia.

Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron-fortified food.

BACKGROUND: Iron and vitamin D deficiencies are two of the most widespread nutritional disorders in the world. Our aim was to know whether the consumption of an iron-fortified fruit juice modifies bone remodelling and the possible influence of baseline vitamin D status on the recovery of iron status in a group of iron-deficient women. METHODS: Iron biomarkers, 25-hydroxyvitamin D levels and dietary intake were measured in 123 iron-deficient menstruating women. A subgroup (n = 41) participated in a randomised double-blind placebo-controlled study of 16-weeks during winter. They consumed a placebo fruit juice (P) or iron-fortified fruit juice (F). Dietary intake, 25-hydroxyvitamin D, parathormone (PTH), bone alkaline phosphatase (ALP), aminoterminal telopeptide of collagen I (NTX) and iron biomarkers were determined. RESULTS: Ninety-two per cent of the iron-deficient women were vitamin D deficient or insufficient. Transferrin saturation and 25-hydroxyvitamin D were positively correlated. Iron status improved in F, 25-hydroxyvitamin D decreased in F and P, and PTH, ALP and NTX levels were within the normal range and did not vary. Women with 25-hydroxyvitamin D ≥ 50 nmol/L compared with 25-hydroxyvitamin D < 50 nmol/L showed a higher increase in transferrin saturation (a marker of iron supply to tissues) during iron recovery. CONCLUSION: The prevalence of vitamin D deficiency or insufficiency is very high in iron-deficient women. The recovery of iron status by consuming an iron-fortified food does not affect 25-hydroxyvitamin D levels; however, the increase in iron supply to tissues is lower if the women also present vitamin D deficiency. Although bone health does not seem to be affected in this group of women, correction of iron and vitamin D deficiencies should be promoted in young women to improve present and future health.

Effects of kalsis, a dietary supplement, on bone metabolism in the ovariectomized rats.

We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (n = 12): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (µCT) in femur and serum osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP), ß-isomer of carboxyterminal telopeptide of collagen I (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase (TRAP) were performed. Treatment with Kalsis prevented BMD loss in OVX group. µCT showed a decrease in BV/TV, and trabecular number, and an increase in trabecular separation in OVX rats. Kalsis administration attenuated partially bone loss observed by µCT due to ovariectomy. BGP, PINP, and the resorption index (CTX/TRAP) were increased in OVX group. Treatment with Kalsis maintained this increase. The mechanism of action of this supplement is not through a decrease in bone remodelling rate. The antioxidant action of this food supplement, due to the synergism of all its components, as a cause of its beneficial effect is suggested.

Characterization of a new experimental model of osteoporosis in rabbits.

To characterize an experimental model of osteoporosis in rabbits induced either by ovariectomy (OVX), glucocorticoids, or by a combination of both. Thirty-five rabbits were randomly allocated into five groups: bilateral OVX, daily methylprednisolone hemisuccinate (MPH) injections at a 1.5 mg/kg/day dose for 4 consecutive weeks (MPH group), or variable dose of MPH between 0.5 and 2 mg/kg/day in combination with OVX (OVX + MPH at low, medium, and high dose). Twenty-two animals were killed 6 weeks after OVX, and 13 were killed 16 weeks later. Dual-energy X-ray absorptiometry was obtained at baseline and 6 and 16 weeks after OVX. High-resolution magnetic resonance imaging (MRI) was carried out at 0 and 6 weeks after OVX. Glucose, total cholesterol, triglyceride, and oestradiol blood levels before and 16 weeks after OVX were determined. Bone mineral density (BMD) decreased significantly at lumbar spine in MPH and OVX + MPH medium-dose groups, and at global knee and subchondral bone of the knee in MPH, OVX + MPH low- and medium-dosage groups (P < 0.05). BMD variations in OVX rabbits were not significant in any of the three anatomical locations analyzed. BMD variation 16 weeks after OVX was significant at lumbar spine and global knee in the OVX + MPH medium-dose group and only at global knee in the OVX + MPH low-dose group (P < 0.05). MRI did not show bone or cartilage changes. Osteoporosis can be induced experimentally in rabbits through isolated MPH or by a combination of OVX and medium dose corticosteroid for 4 weeks. OVX alone was not sufficient to induce osteoporosis.

Bone remodelling is not affected by consumption of a sodium-rich carbonated mineral water in healthy postmenopausal women.

This study was designed to investigate the possible effects of consuming Na-rich carbonated mineral water on bone remodelling and urinary mineral excretion in postmenopausal women. Women (n 18) included were amenorrhoeic (>1 year), healthy and not obese (BMI <30 kg/m2). No woman was taking oestrogen replacement therapy, mineral and vitamin supplements, phyto-oestrogens or medications known to affect bone and lipid metabolism. In two consecutive interventions that lasted 8 weeks each, women drank 1 litre of control mineral water daily and 1 litre of carbonated mineral water, rich in Na, HCO3- and Cl-, daily. Body weight and height were measured, BMI was calculated and blood pressure was measured. Blood samples were taken from fasting subjects and serum obtained to analyse the biochemical bone markers, procollagen I amino-terminal propeptide (PINP) and beta-carboxy-terminal telopeptide of collagen (beta-CTX). At the end of each period, 24 h urine samples were collected to determine Ca, Mg, P, Na+, K+, Cl-, urine excretion and urinary pH. No changes in body weight, BMI or blood pressure were observed during the experimental period. Ca excretion was lower after the intake of carbonated water than after intake of the control water (P=0.037) while P excretion was higher (P=0.015). Total urine, Na and Cl- excretion did not differ between the two periods but urinary pH was increased after the intake of carbonated mineral water. PINP and beta-CTX did not differ between the two periods. Daily consumption of 1 litre of Na-rich carbonated mineral water for 8 weeks does not affect bone remodelling in healthy postmenopausal women.