Sex hormone status may modulate rate of expansion of proximal femur diameter in older women alongside other skeletal regulators.

Context: Little is known of associations between hip geometry and skeletal regulators. This is important because geometry is a determinant of both hip function and resistance to fracture.

Objective: We aimed to determine the effects of sex hormone status and other candidate regulators on hip geometry and strength.

A prospective study of change in bone mineral density over one year in adults with cystic fibrosis.

Background: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. To identify appropriate therapeutic strategies and the optimal time for intervention, it is necessary to document the natural history of cystic fibrosis related low BMD.

Methods: 114 adults with cystic fibrosis underwent bone densitometry a median (25-75% interquartile range) of 12 (12-13) months after initial assessment of bone density.

The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India.

Aims: To compare the vitamin D status of 34 children, 9-24 months old, living in an area of Delhi renowned for high levels of atmospheric pollution (Mori Gate), with a comparable age matched group of children from a less polluted (Gurgaon) area of the city.

Methods: Serum concentrations of calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Haze scores, regarded as a surrogate marker of solar UVB radiation reaching ground level, were measured in both areas.

Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.

Aims/hypothesis: The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy.

Methods: Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial.

Vitamin D nutrition and bone disease in adults.

The consequences of vitamin D deficiency upon the skeleton are well known and management in the absence of renal failure is relatively straightforward. Vitamin D, either by mouth or parenterally will correct the deficiency and heal the osteomalacia. The mechanisms underlying the causation of vitamin D deficiency are now better understood and indicate the importance of underlying calcium malabsorption and secondary hyperparathyroidism leading to 1,25(OH)2D-induced catabolism of 25(OH)D and possibly also of vitamin D itself.

Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes.

Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats.

Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis.

Background: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. The aim of this study was to assess the effect of intravenous pamidronate on BMD in these subjects.

Methods: Patients were invited to participate if they had a BMD Z score of -2 or less in the lumbar spine, proximal femur, or distal forearm.

The role of insulin-like growth factor I in age-related changes in calcium homeostasis in men.

The aim of this study was to evaluate hormonal influences on age-related changes in calcium homeostasis in men. We recruited 178 healthy men, ages 20-79 (about 30 per decade). We measured serum calcium, phosphate, urinary calcium, and creatinine clearance.

Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure.

Background: Resistance to the action of parathyroid hormone (PTH) has been demonstrated in end-stage renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is unknown. However, altered regulation of cellular PTH/PTH-related protein (PTH/PTHrP) receptor (PTH1R) has been assumed to be important.

1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo.

Modulation of angiogenesis is now a recognized strategy for the prevention and treatment of pathologies categorized by their reliance on a vascular supply. The purpose of this study was to evaluate the effect of 1 alpha,25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3)], the active metabolite of vitamin D(3), on angiogenesis by using well-characterized in vitro and in vivo model systems. 1,25(OH)(2)D(3) (1 x 10(-9) to 1 x 10(-7) mol/L) significantly inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell sprouting and elongation in vitro in a dose-dependent manner and had a small, but significant, inhibitory effect on VEGF-induced endothelial cell proliferation.

Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy.

Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations.

Low bone mineral density in adults with cystic fibrosis.

Background: Patients with cystic fibrosis have several risk factors for the development of low bone mineral density (BMD). To identify the prevalence and clinical correlates of low BMD in adult patients with cystic fibrosis, densitometry was performed in 151 patients (83 men) aged 15-52 years.

Methods: BMD was measured in the lumbar spine (L1-4) using dual energy x ray absorptiometry (DXA) and quantitative computed tomography (QCT).

Hip fracture and bone histomorphometry in a young adult with cystic fibrosis.

A 25-yr-old male with cystic fibrosis sustained a fragility fracture of the left femoral neck, which required surgical correction. He had several risk factors for the development of low bone density and despite treatment with an oral bisphosphonate, his bone mineral density reduced further. The patient died 2 yrs after sustaining the fracture.

Prostaglandin E2 regulates vitamin D receptor expression, vitamin D-24-hydroxylase activity and cell proliferation in an adherent human myeloid leukemia cell line (Ad-HL60).

The effects of prostaglandin E2, forskolin, and phorbol 12-myristate 13-acetate on cell proliferation, cell surface antigen expression, vitamin D-24-hydroxylase activity and vitamin D receptor (VDR) expression have been studied in an adherent variant (Ad-HL60) of the human HL60 promyelomonocytic leukemia cell line. Ad-HL60 cells have a more differentiated phenotype than the nonadherent HL60 cells from which they were derived and, unlike the parent cell line, constitutively express vitamin D-24-hydroxylase activity. Treatment of Ad-HL60 cells with 1 microM PGE2 resulted in a decrease in the rate of cell proliferation (cell numbers were approximately 23% of control values after 72 h treatment), a change in expression of leukocyte surface antigens (decreased CD13 and CD14, increased CD11b and CD49d expression), an increase in the synthesis of 24,25-dihydroxyvitamin D3 from substrate 25-hydroxyvitamin D3 (control 5.

Vitamin D receptors in the rheumatoid lesion: expression by chondrocytes, macrophages, and synoviocytes.

Objectives: The active form of vitamin D3, 1 alpha,25 dihydroxyvitamin D3 (1,25D3), through its interaction with vitamin D receptors (VDR), is reported to effect a variety of anabolic and catabolic events, especially in bone and cartilage tissues. As cartilage degradation and tissue remodelling are characteristic features of the rheumatoid lesion, the distribution and expression of VDR at sites of cartilage erosion was examined.

Methods: Immunolocalisation techniques using a rat monoclonal antibody to VDR and an alkaline phosphatase conjugated avidin/biotin detection system were used to examine VDR in 18 specimens of cartilage-pannus junction, 10 specimens of rheumatoid synovium or cartilage tissue, and four primary cultures of adherent rheumatoid synovial cells (RSC).

Autocrine control of vitamin D metabolism in synovial cells from arthritic patients.

Objective: This study was designed to investigate whether 1, 25-dihydroxyvitamin D3 (1,25-(OH)2D3), produced by activated synovial fluid macrophages, promotes its own catabolism by upregulating vitamin D-24-hydroxylase (24-OHase) in synovial fibroblasts through a vitamin D receptor (VDR) mediated mechanism.

Methods: Synovial macrophages and fibroblasts were derived from patients with rheumatoid arthritis. Expression of VDR and 24-OHase mRNAs was determined using in situ hybridisation.

Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.

Pseudovitamin D-defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1alpha-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain.

Bone loss in celiac disease is related to secondary hyperparathyroidism.

Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss.

Expression of genes involved in calcium absorption in human duodenum.

Background: The role of vitamin D metabolites in the regulation of expression of genes involved in dietary calcium absorption by the human intestine remains poorly understood despite much work in animals.

Materials And Methods: To investigate this, we measured the expression of transcripts for two of these genes, calbindin-D9k and the basolateral membrane calcium pumping ATPase, PMCA1, in duodenal endoscopic biopsies from 40 subjects. Northern blots were hybridized with previously characterized probes, and the signal was quantified by phosphor imaging.

Surface-associated protein from Staphylococcus aureus stimulates osteoclastogenesis: possible role in S. aureus-induced bone pathology.

Objective: Staphylococcus aureus is the cause of bone destruction in osteomyelitis, bacterial arthritis and orthopaedic implant failure. We have previously shown that gentle saline extraction of S. aureus has revealed the presence of an extremely potent stimulator of osteoclast activation in both the murine calvarial bone resorption assay and the isolated chick osteoclast resorption assay.

Detection of canine distemper virus in 100% of Paget's disease samples by in situ-reverse transcriptase-polymerase chain reaction.

Previous evidence implicating paramyxoviruses in the aetiopathology of Paget's disease of bone has been controversial. While several groups have demonstrated the presence of paramyxoviruses using electron microscopy, immunohistochemistry, and molecular biological techniques, others have found no evidence of viruses using reverse transcriptase-polymerase chain reaction (RT-PCR). We have previously provided evidence that canine distemper virus (CDV) is present in approximately 65% of samples of pagetic bone, using in situ hybridization and RT-PCR; however, these results have been criticized.

Ascorbic acid-induced chondrocyte terminal differentiation: the role of the extracellular matrix and 1,25-dihydroxyvitamin D.

Chondrocyte terminal differentiation is associated with cellular hypertrophy increased activity of plasma membrane alkaline phosphatase and the synthesis of collagen type X. The hypertrophic phenotype of cultured chondrocytes can be stimulated by ascorbic acid but the underlying mechanisms for this phenotypic change are unclear. As ascorbic acid is central to many hydroxylation reactions, the possibility was examined that its pro-differentiating effects are mediated by its effects on collagen and vitamin D metabolite formation.