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Biomedical subjects

M N Beneton

Publications and source records attributed to M N Beneton.

At least 19 recordsLinked to original sources
PubMed2000

Is a calculated total hip BMD of clinical use?

The diagnosis of osteoporosis is based on bone mass measurement. To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the standard measurement site. This information is not available for many early measurements. We have assessed whether it is possible to derive clinically useful information about total hip bone mineral density (BMD) from measurements at other hip sites. The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were reviewed. The total hip BMD as directly measured was compared with that obtained from the formula: Total hip BMD = 0.48 x Neck BMD + 0.62 x Trochanteric BMD + 0.03. In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods. In the pretreatment state there was good agreement between the two measures (r2 = 0.96, SEE 0.012 g/cm2). If the formula was used to compute a change in total hip BMD, the agreement between both methods remained good. However, the standard error of the estimate of the change represented 59% of the observed change. This indicates that the error associated with this estimate is too great to allow clinically meaningful conclusions to be drawn from calculated total hip BMD. We conclude that, whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip, these estimates are too imprecise to allow conclusions about change in BMD to be made.

Absorptiometry, Photon↗
PubMed1997

Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis.

Postmenopausal women with established vertebral osteoporosis were studied for 2 years to determine the terminal elimination half-life and the duration of response to treatment with intravenous alendronate (30 mg) given over 4 days. The urinary excretion of alendronate followed a multiexponential decline. Approximately 50% of the total dose was excreted over the first 5 days, and a further 17% was excreted in the succeeding 6 months. Thereafter, there was a much slower elimination phase with an estimated mean terminal half-life of greater than 10 years (n = 11). Urinary excretion of hydroxyproline and calcium decreased significantly from pretreatment values by day 3, reaching a nadir by 1 week (40% and 67% decrease, respectively). Thereafter, hydroxyproline remained suppressed for the following 2 years. In contrast, urinary calcium excretion returned gradually toward pretreatment values over the first year and during the second year was comparable to pretreatment values. Serum activity of alkaline phosphatase activity decreased over 3 months (23% reduction), increased gradually thereafter, and returned to pretreatment values at month 24. Bone mineral density measured at the spine increased by approximately 5% during the first year and remained significantly higher than pretreatment values at 2 years. We conclude that a short course of high doses of intravenous alendronate is associated with a prolonged skeletal retention of the agent. This open study also suggests that this regimen has a sustained effect on bone turnover persisting for at least 1 year.

Aged↗
PubMed1996

Clodronate and osteoporosis.

Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and the hypercalcaemia of malignancy. Their undoubted efficacy and relatively low toxicity makes them attractive candidates for the management of osteoporosis. The three bisphosphonates widely tested are etidronate, pamidronate and clodronate. Whereas pamidronate can only be given by intravenous infusion, clodronate may be given intravenously or by mouth. Unlike etidronate, even high doses of clodronate do not impair the mineralisation of bone, making it suitable for long-term use in osteoporosis. Clodronate has been shown to inhibit experimentally induced increases in bone resorption and in patients prevents bone loss at the menopause and during immobilisation. Short-term and long-term studies indicate that clodronate appears to stop bone loss at the lumbar spine in patients with vertebral osteoporosis. Long-term studies of the effects at the hip are not yet reported. The effects of clodronate on the frequency of osteoporotic fractures are not yet known and will demand well controlled long-term prospective studies.

Administration, Oral↗
PubMed1995

Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS: Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

Adolescent↗
PubMed1995

Acute effects of deflazacort and prednisone on rates of mineralization and bone formation.

The aims of this study were to determine (1) whether acute suppression of bone formation could be evaluated after the administration of corticosteroids in man by quantitative bone histomorphometry; and (2) whether there were significant differences between the effects of prednisone and its analog deflazacort. Thirteen patients who needed high-dose corticosteroid therapy were randomly allocated to two groups of treatment (prednisone or deflazacort). Quantitative bone histomorphometry, using the technique of triple labeling, and biochemical measurements of bone turnover were studied. There were no differences in biochemical indices of bone turnover between prednisone and deflazacort at the beginning and end of the 15 days of treatment course. During corticosteroid treatment, there were no significant changes in biochemical indices of bone turnover but a significant decline in total alkaline phosphatase (P < 0.01). Histomorphometric indices, as revealed by measurements of tetracycline interval and extent of labeling, showed no significant differences in either mineral apposition rate or bone formation rate in the two groups. We conclude that the acute glucocorticoid suppression of bone turnover by glucocorticoids is not detectable within the first 2 weeks of treatment by histomorphometric techniques. No differences in bone effects of prednisone and deflazacort were detected in this short-term study.

Adult↗
PubMed1994

Serum type I procollagen peptide: a non-invasive index of bone formation in patients on haemodialysis?

The value of serum procollagen peptide (PICP) as a non-invasive index of bone formation was studied in 18 patients established on haemodialysis. There was a significant correlation between PICP and serum alkaline phosphatase activity (ALP; r = 0.55, P < 0.05), and between PICP and osteocalcin (r = 0.53, P < 0.05). PICP also correlated significantly with histomorphometric indices of bone formation, particularly bone formation rates (BFR) as estimated by the tetracycline double-labelled technique (r = 0.74, P < 0.01), but not with those of bone resorption. There was a similar relationship between BFR and ALP. From the regression analyses, a normal BFR was associated with normal PICP values despite the absence of renal function, suggesting that the impact of renal function on serum concentrations of PICP may not be large. Seven patients had histochemical evidence for significant aluminum overload. In these patients the expected suppression in biochemical and histological indices of bone formation was associated with inappropriately raised PICP concentrations. The mechanism of this discrepancy is not clear, but caution is advocated in the interpretation of PICP in the presence of significant aluminium overload. Our findings otherwise suggest that PICP may be a useful non-invasive index of bone formation in patients on haemodialysis.

Adolescent↗
PubMed1993

Rationale for the use of clodronate in osteoporosis.

Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and in the hypercalcemia of malignancy. Because of their undoubted efficacy and relatively low toxicity, bisphosphonates are attractive candidates for the management of osteoporosis. Clodronate, one of the many bisphosphonates being tested in osteoporosis, may be given intravenously or by mouth. In contrast to etidronate, even high doses of clodronate do not impair the mineralization of bone, making it suitable for long-term use in osteoporosis. As do all the bisphosphonates tested thus far, clodronate appears to delay the rate of bone loss in osteoporosis. Long-term studies are relatively few, so that its steady-state effects on bone mass are not yet known. Most data suggest clodronate is capable at least of delaying the rate of bone loss, but several pilot studies with this agent suggest that increments of bone mass might be sustainable for several years. Clodronate is likely to decrease the frequency of osteoporotic fractures, but there is no evidence for this at present. Well-controlled, long-term prospective studies are needed.

Bone Remodeling↗
PubMed1993

Comparative effects of clodronate and calcitonin on bone in metastatic breast cancer: a histomorphometric study.

We studied the effects of long-term treatment with clodronate, calcitonin or placebo on bone in 36 normocalcaemic women with osteolytic metastases due to breast cancer. Clodronate (1.6 g daily given to 12 patients) induced a significant decrease in osteoclast surface and osteoclast number, and a significant fall in serum calcium and urinary excretion of calcium and hydroxyproline, an effect not noted after treatment with calcitonin (100 U in 12 patients) or in 12 placebo-treated patients. Treatment with clodronate did not abnormally suppress bone turnover nor impair mineralisation, as measured by bone formation and mineral apposition rates.

Adult↗
PubMed1993

Distinction between focally accelerated bone formation and osteomalacia in carcinoma of prostate metastasised to bone.

We studied the histological indices of skeletal turnover in 40 patients with carcinoma of the prostate and skeletal metastases in order to determine the prevalence of osteomalacia. In 20 patients biopsied through uninvolved bone, the histological indices of bone turnover were normal. In particular, osteoid seam width and bone formation rates were consistently normal, indicating the absence of osteomalacia. In biopsies from tumour-laden bone, hyperosteoidosis was present, usually associated with increased amounts of woven collagen and consistently associated with high rates of bone formation and mineralisation. It was concluded that hyperosteoidosis in prostatic cancer is rarely due to osteomalacia.

Adult↗
PubMed1992

Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption.

We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption--as judged by the eroded surface--increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.

Alkaline Phosphatase↗
PubMed1991

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.

Adult↗
PubMed1990

Treatment of Paget's disease of bone with aminohydroxybutylidene bisphosphonate.

This study examined the effects of aminohydroxybutylidene bisphosphonate in 30 patients with Paget's disease of bone, administered as an intravenous infusion for 5 consecutive days. Treatment (5 mg IV daily) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 50% of pretreatment values within 2 weeks and was followed by a similar, but later, decline in the serum activity of alkaline phosphatase. Disease activity remained suppressed throughout the 6 months of observation, and only 1 patients showed biochemical signs of an early relapse. Symptomatic improvement was noted in 27 of the 30 patients. Bone biopsies, undertaken in 10 patients, indicated no adverse effects on mineralization. Transient falls were noted in the total white cell count, particularly the lymphocyte and neutrophil fractions, and were associated with short-lived fever in 3 patients. We conclude that short courses of intravenous AHButBP provide a promising treatment for active Paget's disease of bone.

Aged↗
PubMed1987

Effects of intravenous etidronate disodium on skeletal and calcium metabolism.

The induction of hypercalcemia in malignant disease is almost invariably associated with increased bone resorption. However, tumor-induced changes in bone formation and renal tubular resorption of calcium are also important factors that induce hypercalcemia in some patients. In addition, alterations in calcium fluxes to and from the extracellular fluid secondary to hypercalcemia are important in maintaining or aggravating the hypercalcemic effects of increased bone resorption. These factors significantly affect the responses to treatment of hypercalcemia with inhibitors of bone resorption. This study examined the relative importance of these factors and the effects of intravenous etidronate disodium (etidronate) in neoplastic bone disease with and without hypercalcemia and in Paget's disease of bone. It is concluded that intravenous etidronate is an effective inhibitor of bone resorption, which accounts in large measure for its effects on serum calcium concentrations. These studies of etidronate in hypercalcemia suggest the response is sustained for several weeks.

Aged↗
PubMed1987

Aminohexane diphosphonate in the treatment of Paget's disease of bone.

We studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long-term control of Paget's disease.

Administration, Oral↗
PubMed1987

Osteopenia in systemic mastocytosis: natural history and responses to treatment with inhibitors of bone resorption.

Studies of a 63-year-old woman with osteopenia due to systemic mastocytosis are reported. Delay in making the diagnosis and the occurrence of coincident medical problems meant that radiographs during a 12-year period were available for study. Skeletal symptoms began 20 years after the skin lesions of mastocytosis first appeared, but once established bone loss was rapid, particularly from cortical bone (estimated at 3.75% pa). Biochemical and histological measurements indicated a "high turnover" bone disease and treatment with inhibitors of bone resorption was assessed. Oral, but not intravenous, clodronate was effective in reducing bone turnover as judged by falls in hydroxyproline excretion (p less than 0.01) and serum alkaline phosphatase (p less than 0.01). Mithramycin and chlorambucil were ineffective. Clodronate may be beneficial in arresting bone loss in this disorder.

Biopsy↗