Objectifs. – L'effet des anticalcineurines sur le métabolisme osseux reste controversé. Nous avons voulu comparer l'action de la ciclosporine-A (CsA) et du tacrolimus (FK506) sur le métabolisme osseux des transplantés rénaux.

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF with (Hyperoxalurics, n=55) or without hyperoxaluria (Normooxalurics, n=57) as well as in 100 healthy male control subjects. Pyridoxal 5'-phosphate serum concentration (S-pyridoxal 5'P) and 24-h urinary excretion of 4-pyridoxic acid (U-4pyridoxic acid) were measured using HPLC; 24-h urinary excretion of oxalate (U-oxalate) was measured concurrently. A subgroup of subjects (40 Hyperoxalurics, 15 Normooxalurics and 50 controls) underwent the same measurements before and after 7-day pyridoxine loading per os (pyridoxine hydrochloride, 300 mg/d). Under usual conditions, U-4pyridoxic acid was similar in the three groups, whereas mean S-pyridoxal 5'P was significantly lower ( p<0.0001) in the Hyperoxalurics (59.6+/-21.2 nmol/L) and in the Normooxalurics (64.9+/-19.7 nmol/L) than in the controls (86.0+/-31.0 nmol/L). No correlation could be found between U-oxalate and U-4pyridoxic acid or S-pyridoxal 5'P. After B6 loading, S-pyridoxal 5'P was still significantly lower in the Hyperoxalurics (415+/-180 nmol/L, p<0.001) and in the Normooxalurics (429+/-115 nmol/L, p=0.036) than in the controls (546+/-180 nmol/L), although there was no difference between groups for U-4pyridoxic acid. No correlation in any group could be found between changes in U-oxalate and changes in U-4pyridoxic acid or S-pyridoxal 5'P. Although there is no vitamin B6 deficiency in ICSF with or without hyperoxaluria, these patients, on average, have lower levels of S-pyridoxal 5'P than healthy subjects. However, this slight decrease does not seem to account for idiopathic hyperoxaluria.

Objectives: To compare the effects of vitamin D analogs versus calcitriol on serum levels of Ca, P and parathyroid hormone (PTH). A compound better than calcitriol should increase the Ca x P product less than calcitriol for an equivalent decrease in PTH levels. Methods: Biological activity of 4 vitamin D analogs, 1,25-(OH)2-16ene- D3 (RO1), 1,25-(OH)2-16ene-23yne-D3 (RO2), 1,25-(OH)2-26,27-hexafluoro-16ene-23yne-D3 (RO3) and 1,25-(OH)2-16ene-23yne-26,27-hexafluoro-19nor-D3 (RO4) was tested vs. calcitriol in parathyroidectomized rats. In a second set of experiments, the effects of RO2, RO4 and calcitriol were studied in 5/6 nephrectomized rats with secondary hyperparathyroidism. Results: In parathyroidectomized rats, all analogs (250 pmol/day) led calcemia to rise after 7 days. In uremic rats, all treatments reduced PTH levels. RO4 revealed toxicity. RO2 was as effective as calcitriol in suppressing PTH in a dose dependent manner. Mean plasma ionized calcium did not change from baseline to day 14 and day 28 on RO2 (250 or 500 pmol/day) whereas it increased significantly on RO2 (1,000 pmol/day) and calcitriol (125 or 250 pmol/day). Increasing the dose of calcitriol led Ca × P to rise more dramatically than increasing the dose of RO2, which appears to have a wider therapeutic window than calcitriol. Conclusion: 1,25-(OH)2-16ene-23yne-D3 (RO2) may represent a novel candidate for the treatment of renal osteodystrophy in humans.

BACKGROUND:Controversy exists about the effects of calcineurin inhibitors on bone metabolism. We decided to compare the effects of CyA vs FK506 on bone metabolism of kidney recipients.PATIENTS AND METHODS:From 94 patients grafted at the University Hospital of Nice between 1996 and 1999 treated either by CyA (N=49) or by FK506 (N=45), we selected 14 pairs (18 M, 10F), matched for gender, BMI, time lapsed since transplantation and gonadal status in females. Patients with>1 transplantation or>1 rejection episode were excluded. Cumulative dose of steroids was recorded. Bone mineral density (BMD) was mesured at heel and forearm, as well as serum concentration of calcium, phosphate, parathyroid hormone (PTH), vitamin D metabolites, C-telopeptide (CTX), creatinine, estradiol as well as Bone Alkaline Phosphatase (BAP) activity.RESULTS:Despite the matching, time on hemodialysis was longer in FK506 group. Cumulative dose of steroids was similar between groups. There was no difference between groups in BMD and biochemical parameters except for estradiol serum levels which were dramatically lower in FK506 than in CsA (P=0,02) and for a trend (p=0,08) for BAP and CTX to be higher in FK506 than in CsA.CONCLUSIONS:BMD is not lower in FK506- than in CsA-treated patients although exposure to hyperparathyroidism was longer and estradiol levels were lower in the FK506 than in the CsA group. These data suggest that FK506 may have a favorable bone effect to compensate for these deleterious factors. This hypothesis remains to be tested in longitudinal studies.

TSH antibody 222 Apparent cortisone reductase deficiency

Aim: To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT). Methods: Twenty patients with PHPT were enrolled after successful PTX and received 1 g calcium per os daily for 1 year. They were randomly assigned either to nasal CT (CT group) or to no treatment. The bone mass was measured using dual-energy X-ray absorptiometry at multiple sites. Results: Eight patients in each group completed the study. After 12 months, the bone mass increased significantly at whole-body level and at lumbar spine in both groups, increased at hip and epiphyses of tibia or radius in the CT group only, and did not change at diaphyses of tibia and radius in either group. Conclusions: Bone mass increases after PTX for PHPT in patients receiving oral calcium. CT may help to restore the bone mass at sites of the appendicular skeleton, where trabecular bone predominates.

BACKGROUND Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear. METHODS Thirty-three patients (14 men, 19 women) with ESRD were followed prospectively for 18 months after kidney transplantation. All patients received prednisone and cyclosporin A (CyA) with (n=18) or without azathioprine. Rejection episodes were treated with boluses of methylprednisolone. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry for the spine, hip and whole body (total, trunk, limbs) at 1, 12, 24, 36, 60 and 75 weeks after kidney transplantation. At the same time, blood was assayed for calcium, phosphorus, intact-PTH, alkaline phosphatase, creatinine and CyA, and 24-h urine was assayed for Ca and P. RESULTS BMD at baseline was low at all skeletal sites in women, but not in men. BMD decreased significantly at the spine (-7.0+/-0.9%, week 24), trunk (-4.8+/-0.5%, week 24), total hip (-4.3+/-1.0%, week 36), whole body (-2.2+/-0.4%, week 36) and limbs (-1.0+/-0.7%, week 74). BMD changes over time followed three different patterns: no change or gain, continuous loss, and NADIR. For the spine and trunk, two thirds of patients had a NADIR pattern with recovery at the end of the study, and one-quarter of patients had continuous bone loss. For the limbs, BMD rose or remained stable (n=20), decreased continuously (n=8) or had a NADIR pattern (n=5). Neither gender nor time on dialysis prior to transplantation influenced BMD changes. Patients with PTH serum concentrations below the median value 1 week after kidney transplantation (109 pg/ml) had continuous bone loss at the whole body or limbs but not at other sites. The cumulative dose of prednisone correlated negatively with BMD changes at the spine (r=-0.39, P<0.03), hip (r=-0.50, P=0.005) and trunk (r=-0.52, P=0.002), but not at the whole body or limbs. CyA levels in blood did not correlate with BMD changes. BMD for the whole body and limbs did not change in the patients receiving azathioprine (n=16; -2.7+/-0.7%, P=0.013) but decreased in the others (-2.8+/-0.9%, P<0.0002). CONCLUSIONS High cumulative prednisone doses are deleterious for the axial skeleton. Low levels of PTH observed 1 week after kidney transplantation are predictive of continuous cortical bone loss.

BACKGROUND High protein intake is an accepted risk factor for renal stone disease. Whether meat protein intake affects oxaluria, however, remains controversial in healthy subjects and in stone formers. This study was designed (1) to test the oxaluric response to a meat protein load in male recurrent idiopathic calcium stone formers (ICSFs) with and without mild metabolic hyperoxaluria (MMH and non-MMH, respectively), as well as in healthy controls, and (2) to seek for possible disturbed vitamin B(6) metabolism in MMH, in analogy with primary hyperoxaluria. METHODS Twelve MMH, 8 non-MMH, and 13 healthy males were studied after five days on a high meat protein diet (HPD; 700 g meat/fish daily) following a run-in phase of five days on a moderate protein diet (MPD; 160 g meat/fish daily). In both diets, oxalate-rich nutrients were avoided, as well as sweeteners and vitamin C-containing medicines. Twenty-four-hour urinary excretion of oxalate was measured on the last day of each period, along with 4-pyridoxic acid (U(4PA)) and markers of protein intake, that is, urea, phosphate, uric acid, and sulfate. Serum pyridoxal 5' phosphate (S(P5P)) was measured after protein loading. RESULTS Switching from MPD (0.97 +/- 0.18 g protein/kg/day) to HPD (2.26 +/- 0.38 g protein/kg/day) led to the expected rise in the urinary excretion rates of all markers of protein intake in all subjects. Concurrently, the mean urinary excretion of oxalate increased in ICSFs taken as a whole (+73 +/- 134 micromol/24 h, P = 0.024) as well as in the MMH subgroup (+100 +/- 144 micromol/24 h, P = 0.034) but not in controls (-17 +/- 63 micromol/24 h). In seven ICSFs (4 MMH and 3 non-MMH) but in none of the healthy controls (P = 0.016, chi square), an increment in oxaluria was observed and considered as significant based on the intra-assay coefficient of variation at our laboratory (8.5%). There was no difference in S(P5P)nd U(4PA)etween the groups after protein loading. CONCLUSION Approximately one third of ICSFs with or without so-called MMH are sensitive to meat protein in terms of oxalate excretion, as opposed to healthy subjects. Mechanisms underlying this sensitivity to meat protein remain to be elucidated and do not seem to involve vitamin B(6) deficiency.

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.

Dual-energy X-ray absorptiometry (DXA) is widely accepted as the reference method for the diagnosis and monitoring of osteoporosis and for assessment of fracture risk, especially at the hip. However, axial-DXA is not suitable for mass screening, because it is usually confined to specialized centers. We propose a two-step diagnostic approach to postmenopausal osteoporosis: the first step, using an inexpensive, widely available screening technique, aims at risk stratification in postmenopausal women; the second step, DXA of spine and hip is applied only to potentially osteoporotic women preselected on the basis of the screening measurement.In a group of 110 healthy postmenopausal women, the capability of various peripheral bone measurement techniques to predict osteoporosis at spine and/or hip (T-score < -2.5SD, using DXA) was tested using receiver operating characteristic (ROC) curves: radiographic absorptiometry of phalanges (RA), ultrasonometry at calcaneus (QUS.CALC), tibia (SOS.TIB), and phalanges (SOS.PHAL).Thirty-three women had osteoporosis at spine and/or hip using DXA. Areas under the ROC curves were 0.84 fur RA, 0.83 for QUS.CALC, 0.77 for SOS.PHAL (p < 0.04 vs RA), and 0.74 for SOS.TIB (p < 0.02 vs RA and p = 0.05 vs QUS.CALC). For a level of sensitivity of 90%, the respective specificities were 67% (RA), 64% (QUS.CALC), 48% (SOS.PHAL), acid 39% (SOS,TIB). In cost-effective two-step strategy, the price of the first step should not exceed 54% (RA), 51% (QUI.CALC), 42% (SOS.PHAL), and 25% (SOS.TIB), respectively, of the cost of DXA of hip and spine.In conclusion, RA, QUS.CALC, SOS.PHAL, and SOS.TIB may be useful to preselect postmenopausal women in whom axial DXA is indicated to confirm/exclude osteoporosis at spine or hip.

The aim of this study was to determine the influence of individual factors on differences in bone mineral density (BMD) using dual X-ray absorptiometry pencil beam (PB) and fan beam (FB) modes in vivo and in vitro. PB.BMD and FB.BMD of 63 normal Caucasian females ages 21-80 yr were measured at the lumbar spine and hip. Residuals of the FB/PB regression were used to assess the impact of height, weight, adiposity index (AI) (=weight/height(3/2)). back tissue thickness, and PB.BMD, respectively, on FB/PB difference. The Hologic Anthropomorphic Spine Phantom (ASP) was measured using the PB and FB modes at two different levels to assess the impact of scanning mode and focus distance. The European Spine Phantom (ESP) prototype, a geometrically well-defined phantom with known vertebral densities, was measured using PB and FB modes and analyzed manually to determine the impact of bone density on FB/PB difference and automatically to determine the impact of edge detection on FB/PB difference.. Population BMD results were perfectly correlated, but significantly overestimated by 1.5% at the lumbar spine and underestimated by 0.7% at the neck, 1.8% at the trochanter, and 2.0% at the total hip, respectively, when using the FB compared with PB mode. At the lumbar spine, the FB/PB residual correlated negatively with height (r = 0.34, p < 0.01) and PB.BMD (r = 0.48, p < 0.0001) and positively with Al (r = 0.26, p < 0.05). At the hip, residual of trochanter correlated positively with weight (r = 0.36, p < 0.01) and Al (r = 0.36, p < 0.01). The FB mode significantly increased ASP BMD by 0.7% compared with PB. Using the FB mode, increasing focus distance significantly (p < 0.001) decreased area and bone mineral content, but not BMD. By contrast, increasing focus distance significantly decreased PB,BMD by 0.7%. With the ESP, the PB mode supplied accurate projected area of the bone (AREA) results but significant underestimation of specified BMD in the manual analysis. The FB mode significantly underestimated PB.AREA by 2.9% but fitted specified BMD quite well. FB/PB overestimation was larger for the low-density (+8.7%) than for the high-density vertebra (+4.9%). The automated analysis resulted in more than 14% underestimation of PB.AREA (low-density vertebra) and an almost 13% overestimation of PB.BMD (high-density vertebra) using FB, In conclusion, FB and PB measurements are highly correlated at the lumbar spine and hip with small but significant BMD differences related to height, adiposity, and BMD, In clinical practice, it can be erroneous to switch fi om one method to another, especially in women with low bone density.

A la menopause, les femmes sont confrontees a la substitution hormonale a long terme. Avec leur medecin, elles doivent en peser le pour (prevention des maladies cardiovasculaires et de l'osteoporose) et le contre (augmentation potentielle du risque de cancer de 'endometre ou du sein). Les modulateurs selectifs des recepteurs des œstrogenes (SERM) sont des agonistes es oestrogenes sur certains organes et des antagonistes sur d'autres. Ils offrent de ce fait aux femmes menapausees une alternative a la substitution hormonale a long terme sans en presenter tous les inconvenients. Parmi les SERM, le raloxifene previent la perte osseuse postmenepausique et induit meme apres deux ans une augmentation de la masse osseuse a tous les sites squelettiques de 1,5 a 2%, contre une perte de 1% sous placeho, Le traitement au raloxifene entraine un profil lipidique tres favorable, uant aux mastodynies, aux saignements vaginaux et a la proliferation endometriale, le raloxifene ne se distinque pas d'un placebo, Au contraire es œstrogenes, il ne stimule pas le tissu mammaire chez la emme menopausee et pourrait diminuer le risque de cancer du sein. Seules les bouffees de chaleur se rencontrent plus souvent sous raloxifene que sous placebo. Conclusion: cette nouvelle classe de molecules represente une alternative interessante au traitement hormonal substitutif classique.

Le present article vise a sensibiliser le lecteur a la necessite economique d'une approche diagnostique de l'osteoporose en trois etapes successives: 1. L'etape clinique, c'est-a-dire la selection par l'anamnese d'une fraction substantielle de femmes sans risque d'osteoporose, ne justifiant aucune investigation complementaire. 2. Le screening large des autres femmes par une technique bon marche et disponible partout, permettant d'exclure avec une forte probabilite la plupart des femmes n'ayant pas d'osteoporose. 3. Le diagnostic de certitude d'osteoporose en centre specialise pour celles chez qui les deux premieres etapes n'ont pas permis d'exclure une osteoporose. Ce diagnostic est base sur l'absorptiometrie des rayons X a double energie (DXA), technique consideree comme l'etaloner en la matiere.

Il est connu que certaines maladies osseuses peuvent provoquer une lithiase renale. A l'inverse, la nephrolithiase calcique idiopathique est associee a des alterations du metabolisme osseux et a une diminution de la densite osseuse. Cet article passe en revue la litterature recente sur les implications osseuses de la nephrolithiase calcique idiopathique et sur ses possibles mecanismes physiopathologiques. Le role de l'alimentation ainsi que celui de certains mediateurs (notamment le calcitriol et certaines cytokines), de meme que l'approche therapeutique sont discutes.

To compare the effects of deflazacort (DEFLA) vs. prednisone (PRED) on bone mineral density (BMD), body composition, and lipids, 24 patients with end-stage renal disease were randomized in a double blind design and followed 78 weeks after kidney transplantation. BMD and body composition were assessed using dual energy x-ray absorptiometry. Seventeen patients completed the study. Glucocorticosteroid doses, cyclosporine levels, rejection episodes, and drop-out rates were similar in both groups. Lumbar BMD decreased more in PRED than in DEFLA (P < 0.05), the difference being particularly marked after 24 weeks (9.1 +/- 1.8% vs. 3.0 +/- 2.4%, respectively). Hip BMD decreased from baseline in both groups (P < 0.01), without intergroup differences. Whole body BMD decreased from baseline in PRED (P < 0.001), but not in DEFLA. Lean body mass decreased by approximately 2.5 kg in both groups after 6-12 weeks (P < 0.001), then remained stable. Fat mass increased more (P < 0.01) in PRED than in DEFLA (7.1 +/- 1.8 vs. 3.5 +/- 1.4 kg). Larger increases in total cholesterol (P < 0.03), low density lipoprotein cholesterol (P < 0.01), lipoprotein B2 (P < 0.03), and triglycerides (P = 0.054) were observed in PRED than in DEFLA. In conclusion, using DEFLA instead of PRED in kidney transplant patients is associated with decreased loss of total skeleton and lumbar spine BMD, but does not alter bone loss at the upper femur. DEFLA also helps to prevent fat accumulation and worsening of the lipid profile.