Cannabinoid receptor type 2 gene is associated with human osteoporosis.

Osteoporosis is one of the most common degenerative diseases. It is characterized by reduced bone mineral density (BMD) with an increased risk for bone fractures. There is a substantial genetic contribution to BMD, although the genetic factors involved in the pathogenesis of human osteoporosis are largely unknown.

Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

Unlabelled: Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion.

Introduction: Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD.

Estradiol and raloxifene decrease the formation of multinucleate cells in human bone marrow cultures.

Estrogen (E2) deficiency is responsible for increased bone turnover in the postmenopausal period, and it can be prevented by estrogen replacement therapy. The way estrogen acts on bone cells is not fully understood. Human bone marrow cell cultures may be a reliable model for studying the action of steroids on osteoclastogenesis in vitro.

Fluoride and strontium accumulation in bone does not correlate with osteoid tissue in dialysis patients.

Background: Osteomalacia is now a rare disease in dialysis patients in developed countries since the withdrawal of aluminium overload. The involvement of fluoride and strontium in the pathogenesis of the disease has been suggested. The aim of this study was to investigate a possible association between osteomalacia in dialysis patients and the fluoride or strontium contents of bone.

Effect of oestradiol on cytokine production in immortalized human marrow stromal cell lines.

Oestrogen deficiency enhances bone osteoclastogenesis and bone resorption. Evidence of cooperation between stromal cells and osteoclast precursors in mice suggests that oestradiol acts by regulating cytokine release from stromal cells. Bone marrow stroma contains multipotent progenitors that give rise to many mesenchymal lineages, including osteoblasts that may regulate osteoclast differentiation.

The visualization and evaluation of bone architecture in the rat using three-dimensional X-ray microcomputed tomography.

Microcomputed tomography allows the true three-dimensional structure of bone to be assessed by a nondestructive analysis. This article describes how this technique has for the first time been applied to rat bone to determine the effects of aging, ovariectomy, and antiresorptive drugs on bone structure and how these results compare with those determined by histological and histomorphometric techniques. During the procedure, a micro X-ray source is directed toward the bone sample.

Pamidronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors.

Human hypercalcemia of malignancy (HHM) is generally due to the release into the circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates osteoclastic bone resorption and renal calcium reabsorption through the activation of a receptor similar to that of PTH (PTH-R). However, there is scarce information about the PTH-R regulation in the setting of the hypercalcemia.

Estrogen stimulates PTHrP but not PTH/PTHrP receptor gene expression in the kidney of ovariectomized rat.

The aim of the present study was to test the hypothesis that the decreased renal tubular reabsorption of calcium observed in estrogen deficiency is associated with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40) during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in untreated OVX animals than in all other groups (P < 0.

Cytokine release from marrow mononuclear cells is negatively correlated to cortical elasticity in non-osteoporotic postmenopausal women.

Activation of bone remodeling is likely to be under the control of mechanical factors acting, in part, through soluble local factors. We therefore investigated a relationship between cytokine production by marrow cells and bone elasticity. We studied 36 non-osteoporotic postmenopausal women undergoing hip arthroplasty for hip arthrosis (mean age: 68 +/- 8 years; lumbar BMD Z-score: +0.

Effects of prostaglandins on human hematopoietic osteoclast precursors.

The effect of prostaglandin E2 (PGE2) on osteoclast (OC) differentiation is unclear, either stimulator or inhibitor, depending on the in vitro system used. This probably reflects indirect mechanisms through intermediate cells. We have investigated the direct effect of PGE2 on human OC differentiation from cord blood monocytes (CBMs) in the absence of stromal cells.

Bone effects of dydrogesterone in ovariectomized rats: a biologic, histomorphometric, and densitometric study.

It has been suggested that progesterone might affect bone metabolism. Dydrogesterone (DD) has a chemical structure very close to that of natural progesterone, without androgenic effects. We compared the effect of a daily treatment with DD and estradiol (E2, 40 micrograms/kg) on 70 female rats (8 weeks old), divided in seven groups: controls; ovariectomized (OVX); OVX + E2, OVX + DD 2.

PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats.

PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats. Growth retardation, hypocalcaemia, hyperphosphataemia, and skeletal resistance to the action of PTH are well known features of advanced chronic renal failure (CRF). It has been suggested that the downregulation of renal and skeletal PTH receptors (PTH/PTHrP-R) could play an important role in the occurrence of these abnormalities.

Short-term local injections of transforming growth factor-beta 1 decrease ovariectomy-stimulated osteoclastic resorption in vivo in rats.

Estrogen deficiency in rats is responsible for increased osteoclastic resorption and a subsequent rapid bone loss. TGF-beta, which is known to have acute effects on bone resorption in several in vitro models, has been shown to be secreted by osteoblastic cells in vitro in response to 17 beta-estradiol, but little is known about its in vivo effects on bone resorption. We therefore decided to investigate the short-term effect of TGF-beta 1 on bone resorption in ovariectomized rats.

Serum pyridinoline as a specific marker of collagen breakdown and bone metabolism in hemodialysis patients.

Type I collagen represents more than 90% of bone matrix. Quantitative analysis of collagen cross-link molecules such as pyridinoline (PYD) provides valuable information on bone resorption rate. We have studied 37 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study.

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3.

Relationship between serum beta 2-microglobulin, bone histology, and dialysis membranes in uraemic patients.

Background: beta 2-Microglobulin (beta 2M) is the main constituent of osteoarticular amyloid deposits in haemodialysis patients. When dialysed with cellulosic (C) membrane such patients present a higher incidence of beta 2M-related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and they have higher serum levels of beta 2M. This could favour beta 2M deposition as amyloid fibrils and/or modify bone and cartilage metabolism.

Osteoclast formation from human cord blood mononuclear cells co-cultured with mice embryonic metatarsals in the presence of M-CSF.

Investigating the potentiality of cord monocytes to differentiate toward osteoclast-like cells (OCL) in vitro, we previously reported that in the presence of 1,25(OH)2 vitamin D3 (1,25-(OH)2D3), multinucleated-cells generated by cord monocyte cultures though displaying morphological features of OCL failed to resorb devitalized bones. We thus hypothesized that full differentiation of cord monocytes toward bone-resorbing cells may require the presence of factors released from and/or direct interactions with living osteogenic cells. In the present study, we tested these hypotheses using two culture systems supporting the development of bone-resorbing cells in the presence of bone matrix.

[Osteogenesis induced by the combination of growth factor, fibrin glue and coral; towards a substitute of autologous bone graft. An experimental study on the rabbit].

A triple mixture of TGF-beta, fibrin glue and natural coral skeleton granules (madreporic calcium carbonate) was tested in a rabbit bilateral cranioplasty model. Three-dimensional CT scan and histomorphometry demonstrated that, at one month and at two months, this association produced significantly more bone tissue than other associations, especially growth factor or coral alone. The rate of mineralization was significantly increased bilaterally in all animals having received TGF-beta.

Potentiation of transforming growth factor (TGF-beta 1) by natural coral and fibrin in a rabbit cranioplasty model.

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor beta (TGF-beta 1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones.

Relationship between the number of resorbing cells and the amount resorbed in metabolic bone disorders.

The relationship between bone-resorbing cells, assessed by the presence of tartrate-resistant acid phosphatases (TRAP) and morphologic indices of bone resorption, was determined in 29 osteoporotic patients (14 postmenopausal females and 15 males) and 15 dialyzed patients. The number of TRAP-positive cells per unit of cancellous bone area (N.Oc/B.

Effect of calcitonin administration on young pig trabecular bone remodeling.

Ten-week-old pigs were treated with 4 different treatment schedules of porcine calcitonin for 2 months. Groups C1 and C4 received continuous treatment: C1 had daily IM injections (4 IU/kg/BW (body weight) each injection), and C4 was infused with a minipump implanted subcutaneously delivering 4 IU/kg/BW/day. Groups C2 and C3 received intermittent calcitonin treatment (each injection 4 IU/kg/BW): C2 was given 1 out of every four days, C3 was injected 5 consecutive days out of 20 days.

Optimal correction of acidosis changes progression of dialysis osteodystrophy.

To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these two subgroups patients were randomly allocated to two therapeutics groups: 10 patients (group A) were dialyzed with the conventional amount of bicarbonate (33 +/- 2 mmol/liter) in the dialysate; the rest of the patients (group B, N = 11) had 7 to 15 mmol/liter sodium bicarbonate added to the dialysate to obtain 24 mEq predialysis bicarbonate plasma levels.

Relationships between histomorphometric features of bone formation and bone cell characteristics in vitro in renal osteodystrophy.

To determine whether abnormal bone cell recruitment or differentiation may be involved in the development of aplastic bone lesion in renal osteodystrophy we have compared histomorphometric parameters of bone formation and in vitro behavior of osteoblastic cells isolated from the trabecular bone surfaces in 37 dialysis patients with osteitis fibrosa, normal bone formation rate, or aplastic bone lesion. The bone cell responses to human PTH-(1-34) (20 nmol/L), as evaluated by intracellular cAMP production, and to 1,25-dihydroxyvitamin D (10 nmol/L), as assessed by osteocalcin synthesis, were not different from normal in patients with low, normal, or high bone formation rates. Osteoblastic cells isolated from patients with a high bone formation rate and markedly elevated serum iPTH and osteocalcin values had a higher than normal DNA replication in primary culture.

Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation.

Aluminum bone disease is a frequent complication of dialysis patients. The deferoxamine (DFO) test has been advocated as a noninvasive procedure for the diagnosis of AI bone lesion. However most of these studies have been performed in symptomatic patients with significant AI bone disease.

Decreased bone formation in osteoporotic patients compared with age-matched controls.

In order to study trabecular bone remodeling in postmenopausal osteoporosis we compared bone biopsies of 44 osteoporotic women aged 50-70 to those of 23 nonosteoporotic women, matched for age, who had a bone biopsy during anesthesia for knee arthritis. Trabecular bone volume, mean wall thickness, osteoblastic surfaces, labeled surfaces, and bone formation rate were decreased in osteoporotic women compared with control women. The osteoclast number and the osteoclastic surfaces were the same in the two groups.