Catherine Kindermans

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.

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.

Glomerular function and microalbuminuria in children with insulin-dependent diabetes

Renal function has been evaluated in 45 diabetic children (age 12.5±4 years) with a mean diabetes duration of 4.9±3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A1C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171±31 and 778±172 ml/min per 1.73 m2) compared with controls (124±18 and 631±128 ml/min per 1.73 m2). Both parameters were strongly correlated (r=0.73;P<0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m2) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 μg/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA1C (r=0.35;P<0.05), to mean (r=0.35;P<0.05) and post-prandial blood glucose (r=0.37;P<0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r=0.62;P<0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population.

Renal functional reserve in children with reduced renal mass: study by two dietary periods.

It has been suggested that the “renal functional reserve” (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (Cin) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.Cin did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.Cin was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m2. Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.

Hyperparathyroidism: the limits of surgery in cases of bone or cardiovascular involvement.

In primary hyperparathyroidism (PHPT), asymptomatic bone disease can be detected by bone densitometry. The bone mineral density is about 10% lower than normal control values, especially in the cortical radius. Without parathyroidectomy, bone mineral density is frequently stable, but a few patients, mostly postmenopausal women, have a significant decrease. Histology shows maintenance of trabecular connectivity but with an increase in cortical porosity. After parathyroidectomy, bone mineral density increases, particularly at the lumbar spine and femoral neck, and the benefit persists after 10 years. The fracture risk is controversial but risk of trabecular bone fracture may be higher than that for controls. The impact of PHPT on survival is also controversial, but highest quartile of serum calcium, osteoporosis, old age, and low lean mass are each associated with a death risk. There is also a debate about the criteria for distinguishing between asymptomatic and symptomatic PHPT and about the bone mineral density threshold that should be used as a basis to recommend surgery. The rate of progression of PHPT is slow but in some cases bone loss progresses, justifying bone mineral density follow-up. The frequency of inadequate follow-up and the cost of nonoperative follow-up are in favor of recommending surgery. With broader indications for surgery, it is mandatory to improve the biochemical diagnosis of PHPT.

Bsm I polymorphism in the vitamin D receptor gene is related to bone collagen turnover in healthy infants

We examined the vitamin D receptor genotypes (BB, Bb and bb) defined by the Bsml restriction endonuclease in relation to biochemical indices of bone metabolism in healthy Caucasian infants. We measured the serum concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) and the urinary excretion of total pyridinoline, free, total and bound deoxypyridinoline, the type I collagen N-terminal and C-terminal cross-linked telopeptides. The concentrations of the urinary indices are expressed relative to creatinine. Subjects with BB genotype had the highest mean concentrations of free, total and bound deoxypyridinoline and of the N-terminal cross-linked telopeptide (PANOVA = 0.0016, 0.0004, 0.0002 and 0.0053, respectively). BB boys had a higher excretion of the C-terminal cross-linked telopeptide than the other genotypes (PANOVA = 0.0253). In a subgroup of homozygotes aged 10 (1) months, BB subjects had the highest levels of the C-terminal cross-linked telopeptide (p=0.03), and of total deoxypyridinoline (p=0.02) and pyridinoline (p=0.06) concentrations. No significant association between the vitamin D receptor genotype and PICP was found. These data suggest that there may be a contribution of the vitamin D receptor genotype to skeletal metabolism in early childhood.

DIAGNOSTIC AND THERAPEUTIC ASPECTS OF CALCIOTROPIC HORMONES

: The measurement of calciotropic hormones may be useful in metabolic bone disease. Assays of intact parathyroid hormone are essential to differentiate between primary hyperparathyroidism and nonparathyroid-mediated hypercalcemia. Vitamin D status is best assessed by measuring serum 25(OH)D. Concentrations of calciotropic hormones should be measured in osteoporotic patients if the degree of osteopenia does not correlate with the risk factors. The decrease in circulating parathyroid hormone in osteoporotic patients treated with vitamin D reflects the success of the vitamin D treatment. Parathyroid hormone is also a potential anabolic agent.

Diagnostic and therapeutic aspects of calciotropic hormones

The measurement of calciotropic hormones may be useful in metabolic bone disease. Assays of intact parathyroid hormone are essential to differentiate between primary hyperparathyroidism and nonparathyroid-mediated hypercalcemia. Vitamin D status is best assessed by measuring serum 25(OH)D. Concentrations of calciotropic hormones should be measured in osteoporotic patients if the degree of osteopenia does not correlate with the risk factors. The decrease in circulating parathyroid hormone in osteoporotic patients treated with vitamin D reflects the success of the vitamin D treatment. Parathyroid hormone is also a potential anabolic agent.