Catherine Cormier

Vitamin D Deficiency and Insufficiency in 2 Independent Cohorts of Patients with Systemic Sclerosis

Objective. To investigate 25-OH vitamin D concentrations in 2 independent systemic sclerosis (SSc) populations from France and Italy. Methods. We studied 156 consecutive SSc patients comparable for demographic characteristics: 90 from Northern France and 66 from Southern Italy. 25-OH vitamin D, intact parathyroid hormone, and serum total calcium and phosphorus were measured in all patients. Vitamin D concentrations < 30 ng/ml were considered insufficiency, while values < 10 ng/ml were classified as deficiency. Results. Vitamin D insufficiency and deficiency rates were very high and comparable between the 2 populations: 74/90 (82%) versus 57/66 (86%) for insufficiency and 29/90 (32%) versus 15/66 (23%) for deficiency, respectively, in the French and Italian patients. They were not influenced by vitamin D supplementation, which was not statistically different in the 2 groups. In the combined populations, a significant negative correlation was found between low vitamin D levels and European Disease Activity Score (p = 0.04, r = −0.17) and an even more significant correlation was found with acute-phase reactants (p = 0.004, r = −0.23 for erythrocyte sedimentation rate), and low levels of vitamin D were associated with the systolic pulmonary artery pressure (sPAP) estimated by echocardiography (p = 0.004). In multivariate analysis, vitamin D deficiency was associated with sPAP (p = 0.02). Conclusion. Vitamin D deficiency was very common in the 2 SSc populations, independent of geographic origin and vitamin D supplementation. This suggests that common vitamin D supplementation does not correct the deficiency in SSc patients, and that a higher dose is probably needed, especially in those with high inflammatory activity or severe disease.

Actualite sur les effets de la vitamine D et l'evaluation du statut vitaminique D.

Knowledge about vitamin D has greatly improved during the last few years. Vitamin D cannot any more be considered as exclusively necessary to prevent ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in the elderly (in association with calcium nutrition) is now well demonstrated and many epidemiologic and laboratory data argue for a role in the prevention of several diseases or anomalies (cancer, auto-immune diseases, cardiovascular events, sarcopenia...). A few intervention studies confirming some of these effects also exist. Vitamin D status can easily be assessed by measuring serum 25 hydroxy vitamin D (25OHD) level. However, many experts have claimed that the population-based reference values for 25OHD are too low and that the cut-off value below which vitamin D insufficiency can be present is somewhere between 20 and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L). The main consequences are that vitamin D insufficiency is highly frequent whereas the currently recommended supplementation doses are not sufficient.

Bone markers in clinical practice.

Although biologic indices of bone turnover are widely accepted as research tools in population-based studies, their clinical utility in the management of the individual patient remains controversial. Their main limitation for a routine clinical use is related to an important biologic variability, which means that large variations (ie, in response to therapy) are needed to consider a difference between two measurements as reflecting a significant biologic change. To date, the most valuable bone markers are serum osteocalcin, bone-specific alkaline phosphatase, and the N-terminal propeptide of type 1 procollagen for bone formation and urinary measurements of the phenazopyridine crosslinks and related telopeptides for bone resorption. New serum assays for both C-telopeptide and N-telopeptide of type 1 collagen seem promising but need extensive validation. Although bone markers provide little information in the diagnosis of osteoporosis, strong evidence now shows that they can predict, albeit imperfectly, the rate of bone loss in menopausal women and the response to some antiresorptive therapies. In some populations, increased bone turnover has been shown to be a strong predictor of fracture risk, independently and to the same extent as low bone density. Whether bone markers are used to monitor the efficacy of (or compliance with) a specific treatment or to identify patients at risk for osteoporosis and thus to target preventive therapy, cost-benefit analysis, and evaluation of the potential improvement in patient outcome are clearly needed before these parameters may be universally accepted as tools to optimize patient care.

Bone Mineral Density Evolution After Successful Parathyroidectomy in Patients With Normocalcemic Primary Hyperparathyroidism

CONTEXT It is unclear whether bone mineral density (BMD) improves in patients with normocalcemic primary hyperparathyroidism (PHPT) after parathyroidectomy (PTX). OBJECTIVE The objective of the study was to evaluate and compare the impact of PTX on BMD change at 1 year in normocalcemic vs hypercalcemic PHPT. DESIGN This was a longitudinal cohort study. SETTING The study took place at a referral center. PATIENTS We included 60 PHPT patients (mean age 64.0 ± 10.1 years), successfully treated by PTX by the same surgeon. Two groups were individualized according to baseline serum total (albumin corrected) calcium: 39 patients with normal baseline serum total calcium (normocalcemic group) and 21 patients with hypercalcemia at baseline (hypercalcemic group). MAIN OUTCOME MEASURE BMD changes 1 year after PTX were measured. RESULTS In the normocalcemic group, BMD increased significantly by +2.3 ± 5.0% at the spine (P = .016) and +1.9 ± 5.7% at the hip (P = .048). In the hypercalcemic group, BMD increased significantly by +4.0 ± 3.8% at the spine (P = .0003) and +3.2 ± 4.2% at the hip (P = .003). There was no difference in these BMD gains between both groups (P > .1). The presence of multiple adenomas or hyperplasia was more frequent in the normocalcemic group than in the hypercalcemic group (P = .04). CONCLUSION Our results indicate for the first time that successful PTX in normocalcemic PHPT patients with osteoporosis is followed with mild but significant BMD improvement at the spine and hip at 1 year, comparable with that observed in hypercalcemic PHPT, suggesting that PTX may be beneficial in normocalcemic PHPT.

Serum vitamin D measurement may not reflect what you give to your patients.

The recognized index of vitamin D (VTD) status is the measurement of circulating concentrations of 25-OH VTD (25VTD). A concentration of 30 ng/ml 25VTD (75 nM) is considered by many experts as the minimum optimal concentration. There is currently a growing interest in VTD far beyond bone and calcium metabolism, including cancer, immunology, and hypertension, which has caused a recent upsurge in requests for 25VTD evaluation, necessitating the need for accurate measurement. We report here the case of a 60-yr-old woman diagnosed as having VTD deficiency (serum 25VTD measured with the automated Roche Elecsys method at 12 ng/ml). She was given a single 600,000U VTD2 oral dose. Because serum 25VTD measured with the same assay 2 wk later was still low (11 ng/ml), she was referred to our unit for extensive laboratory testing. All biochemical parameters were normal, including 25VTD (50 ng/ml), but this time the Diasorin radioimmunoassay (RIA) was used to quantify 25VTD. To study the cause for these discrepant results further, we conducted measurements of 25VTD by a specific liquid chromatography-mass spectrometry (LC/MS/MS) method. The LC/MS/MS method separates and quantifies 25hydroxylated metabolites of both VTD2 and VTD3, which are summed to get the total 25VTD concentration. The LC/MS/MS is considered by many as the candidate reference method for 25(OH)D measurement, although drawbacks because of the recognition of other compounds such as epimers have been highlighted, especially in pediatric subjects. In addition to the index case, all three methods were used to measure 25VTD in serum collected from 11 healthy subjects (5 men and 6 women; age, 21–62 yr) before (D0) and 7 and 28 days after a single 600,000U VTD2 dose to mimic the above-mentioned case. Pooling the results from the three time-points, we found that the LC/MS/MS results were highly correlated with the RIA values (Spearman’s 0.94; p < 0.0001) but not with the Elecsys values ( 0.16; not significant). On day 0, the mean concentration [SD] was similar with the three assays (Diasorin RIA: 29.3 [6.8] ng/ml; Roche Elecsys: 30.2 [6.0] ng/ml; LC/MS/MS: 27.8 [6.0] ng/liter). At day 7, 25VTD increased similarly when measured by the Diasorin RIA and LC/MS/MS assays (77.5 [22.2] and 78.4 [22.8] ng/ml, respectively) but decreased (to 27.4 [5.4] ng/ ml) with the Roche Elecsys assay. All subjects had a 25VTD concentration >30 ng/ml with LC/MS/MS and the Diasorin RIA, whereas this was the case in only two of them with the Elecsys. At day 28, 25VTD remained >30 ng/ml in all subjects when measurements were conducted by Diasorin RIA (52.0 [20.3] ng/ml) and LC/MS/MS (52.8 [8.5] ng/ml), whereas it was <30 ng/ml (21.4 [4.9] ng/ml) in all subjects with the Elecsys assay (Fig. 1). The LC/MS/MS data confirmed that the increases observed were solely caused by an increase in the 25VTD2 metabolite. The supplementation with 600,000 IU of VTD2 did not produce a significant rise in calcium and phosphorus levels (2.35, 2.35, and 2.39 mM, respectively, for day 0, 7, and 28 median calcium levels and 1.07, 1.05, and 1.06 mM, respectively, for phosphorus concentrations at the same times). We did not observe any significant variation in parathormone levels (41 versus 44 pg/ml before and after 28 days, respectively). Whereas skin exposure to UVB produces VTD3 and the food sources of VTD are mainly VTD3, supplementation is still often made with VTD2, especially in the United States. Several experts recommend exclusive use of VTD3, (7) because it has been reported that VTD3 maintains an adequate 25VTD concentration for a longer period than VTD2. (8) This recommendation has been recently challenged, and the choice of the best vitamin D supplement requires further study. Thus, as long as VTD2 is available (and prescribed), it is mandatory to measure 25VTD with a method that recognizes both 25VTD2 and 25VTD3. This is the situation if LC/MS/MS or the Diasorin RIA is used, whereas the Roche Elecsys assay exclusively measures 25VTD3. The case briefly described above shows that measuring 25VTD with an assay exclusively specific for 25VTD3, such as the Roche Elecsys assay, underestimates VTD status in patients supplemented with VTD2. This can potentially cause overtreatment, leading to further expensive and stressful studies. The authors state that they have no conflicts of interest.

Vitamin D and primary hyperparathyroidism (PHPT).

Vitamin D deficiency and PHPT are two common conditions, especially in postmenopausal women. Vitamin D deficiency is said to be even more frequent in PHPT patients than in the general population due to an accelerated conversion of 25OHD into calcitriol or 24-hydroxylated compounds. Although several studies have reported worsening of PHPT phenotype (larger tumours, higher PTH levels, more severe bone disease) when vitamin D deficiency coexists whereas vitamin D supplementation in PHPT patients with a serum calcium level<3 mmol/L has been shown to be safe (no increase in serum or urinary calcium) and to decrease serum PTH concentration, that many physicians are afraid to give vitamin D to already hypercalcemic PHPT patients. On the other hand, it is possible that, in some patients, a persistent vitamin D deficiency induces, in the long-term, an autonomous secretion of PTH (i.e. tertiary hyperparathyroidism). The mechanism by which this could occur is unclear however. Finally, as many, otherwise normal, subjects with vitamin D insufficiency may have an increased serum PTH level we believe that those with vitamin D insufficiency should be excluded from a reference population for serum PTH levels. By doing that, we found that the upper normal limit for serum PTH was 25-30% lower than in the whole population.

Increased risk of osteoporosis and fracture in women with systemic sclerosis: A comparative study with rheumatoid arthritis

To investigate whether women with systemic sclerosis (SSc) have an increased risk of osteoporosis (OP) and related fractures compared to a high‐risk population with rheumatoid arthritis (RA) and also healthy controls, and to determine putative specific OP and fracture risk factors.

When should we measure Vitamin D concentration in clinical practice

Abstract The many recently published data on vitamin D have raised much interest in the medical community. One of the consequences has been a great increase in the prescription of vitamin D concentration measurements in clinical practice. It must be reminded that only the measurement of 25-hydroxyvitamin D (25(OH)D) concentration is indicated to evaluate vitamin D status. Furthermore, since vitamin D insufficiency is so common, since treatment is inexpensive and has a large safety margin, and since we already have much data suggesting that besides its classic effects on bone and mineral metabolism, vitamin D may potentially be helpful for the prevention/management of several diseases, perhaps should it be prescribed to everyone without prior testing? In our opinion, there are however groups of patients in whom estimation of vitamin D status is legitimate and may be recommended. This includes patients in whom a “reasonably” evidence-based target concentration (i.e., based on randomized clinical trials when possible) should be achieved and/or maintained such as patients with rickets/osteomalacia, osteoporosis, chronic kidney disease and kidney transplant recipients, malabsorption, primary hyperparathyroidism, granulomatous disease, and those receiving treatments potentially inducing bone loss. Other patients in whom vitamin D concentration may be measured are those with symptoms compatible with a severe vitamin D deficiency or excess persisting without explanation such as those with diffuse pain, or elderly individuals who fall, or those receiving treatments which modify vitamin D metabolism such as some anti-convulsants. Measurement of Vitamin D concentrations should also be part of any exploration of calcium/phosphorus metabolism which includes measurement of serum calcium, phosphate and PTH.

High third generation/second generation PTH ratio in a patient with parathyroid carcinoma: clinical utility of third generation/second generation PTH ratio in patients with primary hyperparathyroidism

Background  Primary hyperparathyroidism (PHP) is caused by parathyroid adenomas or hyperplasia, and occasionally by parathyroid carcinoma. Recently a high third generation/second generation PTH ratio has been observed in some patients with parathyroid carcinoma.

Inhaled beclomethasone and bone metabolism in young asthmatic children: A six-month study

vaccine recipients had IgE ant ibody to gelatin. Animal gelatin has long been used as a stabilizer in not only live virus vaccines but also inactivated vaccines; it was believed to have no antigenicity to human beings. To prevent gelatin anaphylaxis on vaccination, al ternat ive stabilizers that have no antigenicity to human beings should be explored. For t r ea tmen t of anaphylaxis, children should stay at the clinic for 30 minutes after vaccination. Prior quest ioning of vaccine recipients and their parents about allergic symptoms associated with ingestion of gelat in-containing foods may be help to prevent anaphylaxis in some children.