Vitamin D and HRT: No benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study

The study was designed to examine the effect of hormone replacement therapy (HRT) and low-dose vitamin D (Vit D) supplementation on the prevention of bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo-controlled study. The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n=13100). A total of 464 early postmenopausal women were randomized to four groups: (1) HRT (a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E₂Val/CPA); (2) vitamin D₃ (cholecalciferol, 300 IU/day); (3) HRT+Vit D; and (4) placebo (calcium lactate; 93 mg Ca²⁺/day). Lumbar (L1–4) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p<0.001) and by 1.4% in the HRT+Vit D group (p=0.002), whereas lumbar BMD had decreased by 3.5% (p<0.001) in the Vit D group and by 3.7% (p<0.001) in the placebo group. The loss of femoral neck BMD was lower in the HRT (–0.3%) and the HRT+Vit D (–0.9%) groups compared with the Vit D (–2.4%) and the placebo groups (–3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone.     

Book reviews

Pediatric Radiology -     

The cortisol awakening response in bipolar illness: a pilot study.

OBJECTIVE: A growing body of data suggests that a significantly enhanced salivary cortisol response to waking may indicate an enduring tendency to abnormal cortisol regulation. Our objective was to apply the response test to a population already known to have long-term hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation. We hypothesized that the free cortisol response to waking, believed to be genetically influenced, would be elevated in a significant percentage of cases, regardless of the afternoon Dexamethasone Suppression Test (DST) value. METHOD: Using the free cortisol response to waking and the short daytime profile, we tested 18 clinically stable, lithium-responsive subjects from our long-term naturalistic follow-up of monthly DSTs. These tests include salivary testing every 15 minutes during the first hour of waking, followed by samples taken at 3:00 PM and 8:00 PM. RESULTS: While clinically stable on lithium prophylaxis, patients with bipolar disorder (BD) showed a significantly enhanced salivary cortisol response to waking, compared with control subjects (P < 0.03). Cortisol levels 30 minutes after waking significantly exceeded those in the large normative data provided in the literature (P < 0.001). CONCLUSIONS: Our observations support the hypothesis that the free cortisol response to waking can reflect relatively enduring HPA dysregulation, even when lithium-responsive BD patients are clinically well and their DSTs are normal. Because the test is easy to administer, the free cortisol response to waking may hold promise as a marker in studies of high-risk families predisposed to, or at risk for, mood disorders.     

Weitere Entwicklung der Krebssterblichkeit in Deutschland bis zum Jahr 2010

Ohne Zusammenfassung     

Non-linkage of the islet amyloid polypeptide gene with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Type 2 (non-insulin-dependent) diabetes is associated with the deposition of islet amyloid. The major formative peptide, islet amyloid polypeptide, has recently been characterised and an abnormality of the structure or expression of this gene is a possible candidate for the inherited component of Type 2 diabetes. A restriction fragment length polymorphism of the gene has been identified with Pvu II. To study the relationship between the islet amyloid polypeptide gene and Type 2 diabetes, two distinct genetic approaches have been undertaken. Firstly, non-linkage has been demonstrated in four pedigrees, with four normoglycaemic first degree relatives having an allele associated with diabetes in other family members, and one affected relative not having the putatively associated allele. The LOD score taking age-related penetrance into account was –1.68, making linkage unlikely (p=0.02). Secondly, in a population-based restriction fragment length polymorphism survey, no linkage disequilibrium of the alleles was found between a population of unrelated Caucasian subjects with Type 2 diabetes and a normal population. A mutation in or near the islet amyloid polypeptide gene is thus unlikely to be a common cause of Type 2 diabetes.     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996