Showing papers by "Jean-Jacques Body published in 1996"
TL;DR: Ibandronate therapy led to a dose-dependent reduction in serum calcium levels and the incidence of drug-associated AEs was low, and a dose escalation of ibandronate can be recommended for further clinical trials.
Abstract: PURPOSETo evaluate the hypocalcemic effect and safety of three different doses of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to identify factors predicting response.PATIENTS AND METHODSOne hundred seventy-four cancer patients with a serum calcium level greater than 2.7 mmol/L (10.8 mg/dL) were enrolled onto the trial. If hypercalcemia persisted after fluid repletion, patients were randomly assigned to treatment with 0.6 mg, 1.1 mg, and 2.0 mg of ibandronate. Response, defined as restoration of normocalcemia, was evaluated by an intent-to-treat analysis.RESULTSOne hundred seventy-three (99%) patients were assessable for toxicity and 151 (87%) for efficacy. The administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (group C) of ibandronate led to response rates of 44%, 52%, and 67%, respectively. Significantly more patients in group C responded than in group A (P = .0276). Of the various parameters examined, only the initial serum calcium level (P < .0001; odds ratio, 0.0...
120 citations
TL;DR: It has been shown that alendronate preferentially goes to sites of active bone resorption and increases the membrane permeability of osteoclasts to Ca++ and other ions such as H+ and NH4+, making them unable to resorb bone.
99 citations
TL;DR: Cyclical pamidronate treatment of postmenopausal osteoprosis appeared to be effective in reducing bone turnover assessed by BGP, ALP and OHPro/Cr, followed by an increase in vertebral BMD.
61 citations
TL;DR: This newly available IRMA for measuring circulating human BGP appears to be quite sensitive, reproducible and robust, and should be especially useful for investigating clinical conditions characterized by a low bone formation rate.
Abstract: The measurement of circulating osteocalcin or bone GLA protein (BGP) constitutes a well established and non-invasive means for evaluating preferentially the bone formation rate, but most available commercial assays suffer from several technical constraints, notably a rapid degradation of BGP at room temperature or after thawing and the inability to measure subnormal values. We evaluated, from a technical and a clinical viewpoint, a newly available two-site sandwich immunoradiometric assay (IRMA) using standard of human origin and two different monoclonal antibodies. The theoretical and functional assay detection limit was 0.3 ng/ml. Concentrations of BGP progressively decreased when the serum was left at 4 degrees C or at room temperature (mean apparent loss of 15% after 24 h). Two cycles of freezing-thawing only lightly reduced the BGP concentrations. The mean (+/- SD) BGP concentration was 19.6 +/- 7.9 ng/ml in healthy subjects (NI, N = 61); the normal range was 8.1-35.6 ng/ml. There was a marked difference between pre- and postmenopausal women: 15.1 +/- 4.4 vs 22.3 +/- 8.4 ng/ml, respectively (p < 0.05). The mean BGP concentration in patients with tumor-induced hypercalcemia (N = 29) was not significantly different from NI, but nine patients (31%) had subnormal levels and five (17%) had elevated BGP levels. Concentrations of BGP were significantly increased in patients with hyperparathyroidism (N = 14) (45.1 +/- 21.0 ng/ml) and significantly lower than NI in patients with hypoparathyroidism (N = 18) (7.3 +/- 4.6 ng/ml). Concentrations of BGP were also measured by a classical radioimmunoassay using bovine standards and tracer; the correlations between both sets of measurements were significant in all groups, except in patients with hypoparathyroidism. In summary, this newly available IRMA for measuring circulating human BGP appears to be quite sensitive, reproducible and robust. It should be especially useful for investigating clinical conditions characterized by a low bone formation rate.
25 citations
TL;DR: It is indicated that MCF-7 breast cancer cells secrete factors which inhibit the growth of OBL and increase their sensitivity to various osteolytic agents.
Abstract: The pathogenesis of breast cancer-induced osteolysis remains largely unknown. To evaluate the potential role of osteoblasts as target cells during this process, we incubated SaOS-2 human osteoblast-like cells (OBL) with culture media conditioned by proliferative (PM, ‘Proliferation Media’) or confluent (CfM, ‘Confluence Media’) MCF-7 human breast cancer cells. CfM decreased the growth of OBL by 26% (P < 0.01) while PM was without significant effect on this parameter. In contrast, both PM and CfM obtained from MCF-7 cultures increased the cyclic AMP (cAMP) response of OBL to the osteolytic agents PTH (10−8 M) and PTH-related peptide (PTHrP, 10−8 M) by a factor of about 3 (P < 0.001), and to prostaglandin E2 (PGE2, 10−6 M) by a factor of about 2 (P < 0.01). No significant modulation of OBL growth or sensitivity to PTH, PTHrP, or PGE2 was induced by media obtained from HBL-100 non-malignant immortalized breast epithelial cell cultures. 17β-estradiol (E2, 10−8 M) and the antiestrogen tamoxifen (Tam, 10−7 M) added for 48 h to MCF-7 cultures before collecting conditioned media attenuated and potentiated, respectively, the PM- but not the CfM-induced increase in the response of OBL to PTH or PTHrP. Along the same line, the addition to MCF-7 conditioned media of a polyclonal anti-transforming growth factor-β (TGF-β) antibody attenuated by about 25% (P < 0.01) the PM-induced increase in OBL response to PTH and PTHrP while abrogating the modulatory effects of E2 and Tam on that response. Together, our results indicate that MCF-7 breast cancer cells secrete factors which inhibit the growth of OBL and increase their sensitivity to various osteolytic agents. TGF-β was only partly responsible for these effects, and accounts for their modulation by E2 and Tam. The identification of other osteoblast-modulatory factor(s) should contribute to a better understanding and treatment of breast cancer-induced osteolysis.
21 citations
TL;DR: Low serum Pi with reduced threshold for phosphate excretion and increased tubular calcium reabsorption supported the notion that PTHrP was indeed the essential mediator of paraneoplastic hypercalcemia in this case despite the extensive bone destruction.
Abstract: Tumor-induced hypercalcemia (TIH) is a frequent complication of advanced cancer, but it has been rarely reported in patients with sarcoma. We describe the case of a young female patient with TIH and with an extensive synoviosarcoma of the left lower limb destroying the bony structures. Hypercalcemia was severe (18.3 mg/dl) and accompanied by low serum Pi and suppressed parathyroid hormone (PTH) and 1,25(OH)2 vit D3 serum concentrations. Hypercalcemia was successfully treated with ibandronate, a new third-generation bisphosphonate, and radical surgery was performed when the patient was normocalcemic. Circulating levels of PTH-related protein (PTHrP) were elevated at 22.5 pmol/L (NI <9) PTHrP levels did not change after successful therapy of TIH, in contrast with PTH, which increased sharply. PTHrP levels were normalized after radical surgery. Moreover, low serum Pi with reduced threshold for phosphate excretion and increased tubular calcium reabsorption supported the notion that PTHrP was indeed the essential mediator of paraneoplastic hypercalcemia in this case despite the extensive bone destruction. © 1996 Wiley-Liss, Inc.
4 citations
TL;DR: It is concluded that following cessation of cyclical etidronate treatment there was no evidence of "frozen bone" as there was a resurgence of osteoblast function and that in many of the patients spine bone density was maintained.
Abstract: AFTER COMPLETION OF CYCLICAL ETIDRONATE TREATMENT A. Fairncy, K. Isaac, PKyd, M. Murphy, E. Thomas and I. Wilson. Imperial College School of Medicine (St. Mary's) and St. Mary's NHS Trust, Paddington, London W2 1PG Cyclical Etidronate treatment is now an established therapy for patients with osteoporosis, and may be used as an alternative to hormone replacement thearpy. However, there is great interest in the possible changes in bone density when treatment is discontinued and whether bone cell function re~urus to its original level. We have undertaken a study to determine whether patients who have a 3 year course of cyclical etidronate, lose the bone they have gained on completion of treatment during the post treatment years, end whether bone remodelling returns to normal 24 patients treated with Didronel PMO (Procter and Gamble) for 3 years were studied at 3 monthly intervals during a treatment free year following completion of treatment; bone densitometry (LUNAR DXA), serum osteocalcin (OSTK-PR CIS RIA) bone alkaline phosphatase (bALP) (Ostasr Hybfitech IRMA) and intact PTH (Nicholls Institute, IRMA) were measured. There was a dramatic rise in osteocalcin and bALP after treatment (mean (SEM) 6.0 (0.5)lJg/l at 3 years, 9.9 (0.6)pg/L at 4 years p<0.001, 10.0pg/l (0.8) and 15.4pg/1 (1.1) p<0.01 respectively). Overall spine BIVID did not fall. (BMD year 0 3 increase 3.57% (1.55) (mean(SEM)) year 3 4 0.7% (1.49). PTH increased slightly but significantly at 3 -4 years. We conclude that following cessation of cyclical etidronate treatment there was no evidence of\"frozen bone\" as there was a resurgence of osteoblast function and that in many of the patients spine bone density was maintained.
1 citations