Abstract-Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54.8Ϯ3.5 (meanϮSD) years who entered this double-blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (nϭ15)

SummaryOBJECTIVE In order to determine if a serious disease like childhood acute lymphoblastic leukaemia (ALL) and the treatment necessary to cure the patients has long term effects on bone mass, we assessed bone mineral density (BMD) and several parameters involved in bone formation in a group of young adult survivors of ALL. DESIGN AND PATIENTS Fourteen male and ten female survivors, treated for ALL in childhood, were cross-sectionally studied, at a mean age of 25·1 years (range 20·1-34·9). All patients, except for two, had received cranial irradiation as part of their treatment (mean radiation dose 2460 cGy).MEASUREMENTS Height and weight were measured. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry in the lumbar spine, femoral neck, femoral trochanter and at 1/3 distal and ultradistal in the radius. Early morning serum levels of LH, FSH, oestradiol or testosterone, IGF-1 and IGF-BP3 were determined as well as several specific markers of bone turnover.RESULTS Mean height, expressed as standard deviation score (SDS) was ¹1·12, significantly reduced. BMD in the lumbar spine, femoral neck and at 1/3 distal and ultradistal in the radius, was significantly lower compared to the reference population (P < 0·05). No correlation was found between the BMD values and the cumulative dose of administered cytotoxic drugs, the age at diagnosis of ALL or the duration of follow-up. Mean IGF-1 and IGF-BP3 SDS-scores were ¹1·24 and ¹0·78 respectively, significantly reduced. GH stimulation tests performed in a subgroup of 9 patients showed an insufficient peak GH response in at least one test in all tested patients. The values of LH, FSH oestradiol or testosterone were within the normal adult range. Serum markers of bone formation and bone resorption were in the normal range, indicating that bone turnover was normal at the time of the study.CONCLUSIONS Bone development in patients cured of acute lymphoblastic leukaemia is disturbed, resulting in a significantly reduced bone mineral density. Impaired growth hormone activity, as a long term effect of cranial irradiation, may be one of the underlying causes as well as the illness itself and the administered cytotoxic drugs. Since a reduced bone mineral density predispose patients to osteoporosis, intervention in order to improve bone mass should be considered.

This study reports a method to describe and analyze the structure of the trabecular pattern seen on radiographs of the distal radius. The structure is measured and related to the bone mineral density (BMD) of the lumbar spine measured by dual-photon absorptiometry. Radiographs of hand and wrist combined with additional information of the bone mineral density of the vertebrae serve as testing material. With a computer-aided imaging system, a part of the depicted radius is scanned. The image is filtered and segmented into a bilevel picture consisting of a light network with dark meshes. Seven features of the bilevel picture are measured and analyzed. It is shown that six features correlate significantly with the bone mineral density measured at the lumbar spine, although the correlations between the trabecular pattern and the BMD are too weak to allow precise predictions of BMD values for individuals. Nevertheless, the correlations confirm the existence of a relationship between the radiographic trabecular pattern and the bone mineral density of the lumbar spine. The method is worth being further developed for use on individual patients. It provides a noninvasive tool to make an objective and quantitative assessment of the trabecular pattern.

In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. The renal tubular cells have an important role in calcium and phosphate metabolism, where the 1a-hydroxylase enzyme metabolizes the conversion of 25 (OH)-vitamin D to potent 1,25 (OH) 2 -vitamin D, whereas the sodium-phosphate transporter controls tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (fibroblast growth factor 23 is the primary phosphatonin candidate), which leads to inhibition of 1a-hydroxylase, and simultaneously to inhibition of the sodium-phosphate transporter domain NPT2c leading to parathyroid hormone-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH) 2 -vitamin D or the vitamin D analog alfacalcidol and elementary phosphorus. Unfortunately, patients with XLH may develop nephrocalcinosis, secondary or tertiary hyperparathyroidism, and in some situations also hypertension and cardiovascular abnormalities. We describe a patient with XLH caused by a novel missense mutation in the PHEX gene, who on treatment with alfacalcidol and oral phosphate had normal growth and minimal bone deformities, but who subsequently developed moderate nephrocalcinosis, significant hyperparathyroidism, hypercalcemia, renal failure, and hypertension. We also report the use of the calcimimetic drug cinacalcet in the successful treatment of hypercalcemia and hyperparathyroidism.European Journal of Endocrinology 159 S101-S105