F. Loré

Long-term treatment with calcitriol in postmenopausal osteoporosis

In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis

SummarySerum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 μg/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3).Basal serum BGP was significantly lower in osteoporotic women (3.8±1.4 ng/ml) than in agematched controls (6.8±2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8±1.5) was significantly higher than the mean basal value.It is known that BGP synthesis is stimulated by 1,25 (OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation.

Endovascular treatment of a cavernous sinus dural arteriovenous fistula by transvenous embolisation through the superior ophthalmic vein via cannulation of a frontal vein

Abstract We describe a new approach for transvenous embolisation of cavernous sinus dural arteriovenous fistulae through the superior ophthalmic vein (SOV), i.e., via percutaneous cannulation of a frontal vein. Modern neurointerventional angiographic materials make it possible to reach the SOV in this way without puncturing it in the orbit or a surgical exposure. Orbital phlebography should still be in the repertoire of interventional neuroradiology units in large centres.

Unilateral renal agenesis in a family with medullary thyroid carcinoma.

To the Editor: Germ-line mutations in the RET proto-oncogene are associated with various disease phenotypes including familial medullary thyroid carcinoma and Hirschsprungs disease.1 Studies have ...

Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.

Loré F, Talidis F, Di Cairano G, Renieri A (Endocrinology Unit; Medical Genetics Unit, University of Siena, Italy). Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations. J Intern Med 2001; 250: 37–42.

Serum levels of 25-hydroxyvitamin D in postmenopausal osteoporosis

SummarySerum concentrations of 25-hydroxyvitamin D were measured in a group of women with symptomatic postmenopausal osteoporosis, assessed by bone biopsy. A competitive protein binding assay was used, which included a chromatographic step. Accurate surveys of dietary or therapeutic vitamin D intake and light environment were obtained in each patient.Women with severe postmenopausal osteoporosis were found to have significantly (P<0.001) higher serum levels of 25-hydroxyvitamin D than age-matched normal women, the mean values being 27.5 ng/ml (±13.6 SD) and 8.2 ng/ml (±5.7), respectively.The authors hypothesize that the reduction in 1,25-dihydroxyvitamin D, recently reported in postmenopausal osteoporotic women, might be responsible for the increased serum levels of 25-hydroxyvitamin D through an inadequate product inhibition of liver vitamin D 25-hydroxylase.

Effect of the administration of 1,25-dihydroxyvitamin D3 on serum levels of 25-hydroxyvitamin D in postmenopausal osteoporosis

SummarySerum concentrations of 25-hydroxyvitamin D were measured in a group of women with symptomatic postmenopausal osteoporosis, before and after long-term treatment with physiological doses of 1,25-dihydroxyvitamin D3. A competitive protein binding assay was used, which included a chromatographic step. The treatment resulted in a significant decrease in serum 25-hydroxyvitamin D levels that were higher than normal in basal conditions, the mean values before and after therapy being 27.7 ng/ml (±17.1 SD) and 19.7 ng/ml (±12.7), respectively. These findings seem to confirm the hypothesis that an inadequate product-inhibition of liver 25-hydroxylase is responsible for the increased basal levels of 25-hydroxyvitamin D found in postmenopausal osteoporosis.

Total body absorptiometry in postmenopausal osteoporosis patients treated with lα-hydroxylated vitamin D metabolites

Skeletal bone can be measured using the techniques of single-photon absorptiometry (SPA), dual-photon absorptiometry (DPA), quantitative cemputed tomography (QCT) and, more recently, dual-energy X-ray absorptiometry (DXA) [1]. DXA systems have a higher radiation flux than conventional 153Gd DPA and provide better precision [2,3]. Total body DXA allows accurate and precise quantitation of bone mineral content (BMD) and bone mineral density (BMD) of the entire skeleton and its major anatomical areas [4,5]. It has been demonstrated that women with postmenopausat osteoporosis generally show an impairment in the active intestinal transport of calcium [6,7] that has been accounted for by a decreased renal lo~-hydroxylation of vitamin D [8,9]. The reduction in 1,25(OH)2D levels cannot be caused by a lack of precursor 25-hydroxyvitamin D [8,101, but rather by impairment synthesis of 1,25(OH)2D. Physiological doses of synthetic 1,25(OH)2D 3 (calcitriol) or of lc~-hydroxylated synthetic analogues, such as 1 o~-hydroxyvitamin I) 3 (alphacalcidol), restore normal calcium absorption in osteoporotic patients [11]. Moreover long-term treatment with calcitriol (1 gg/ day) demonstrated significant benefits without untoward adverse effects [ 12,14]. Similar results have been achieved with 1,24(OH)2 vitamin D 3 [15] and lc~-OH vitamin D 3 (alphacalcidol) [ 16], indicating that these effects could be accounted for by the hydroxyl group at carbon atom 1 of the A ring.

Effects of lα-Hydroxylated Vitamin-D Metabolites on Intestinal Radio-Calcium Absorption and Urinary Calcium Excretion in Short- and Long-Term Treatments of Postmenopausal Osteoporosis

Synthetic lα-hydroxylated vitamin D metabolites, lα-OHD3 and 1, 25(OH)2D3, have been successfully used in the management of postmenopausal osteoporosis. Dramatic results have been maintained in terms of increases in intestinal radiocalcium absorption in short- as well as in long-term treatment procedures in terms of increases in bone mineral content and decreases in the occurrence of vertebral fractures.