Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I

in Calcified Tissue International (2001), 69(3), 130-137

Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an ... [more ▼]

Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an antiresorptive therapy (monitoring tool). Our aim was to assess the ability of four currently marketed biochemical markers of bone resorption, based on the measurement of degradation products from collage type I telopeptides to monitor the elevated resorption associated with menopause. Women (846) were stratified for menopause, age, and bone mineral density and the following markers were measured: urinary cross-linked N-telopeptides of type I collagen (NTx), the levels of breakdown products of type I collagen C-telopeptides in serum (S-CTx), and in urine, by ELISA (U-CTx-E), and RIA (U-CTx-R). Furthermore, the ratio (a/b) between the aL form of CTx measured in the CTx RIA and the bL form measured in the ELISA was calculated. The mean difference was calculated for each marker in women with osteopenia (Op) or osteoporosis (PMO) (WHO definition) compared with healthy premenopausal (Pre) women and postmenopausal (N Post) women with normal bone mass. Serum CTx showed the highest elevation in post- compared with premenopausal women. All marker values were significantly higher in Op and PMO subjects compared with both Pre and to N Post women. Compared with premenopausal values, the largest elevation in both Op and PMO women was observed for serum CTx. Compared with N Post, urine NTx showed the highest increase in OP subjects. The a/b CTx ratio was elevated in post- compared with Pre women, but there was no difference in the ratio among N Post, Op, or PMO women. In conclusion, postmenopausal women showed elevated turnover with all bone resorption markers, but with substantial individual variation in resorption levels. Furthermore, the turnover process in postmenopausal women appears to be quantitatively different from the premenopausal stage, apparent as altered a/b CTx ratios. [less ▲]

Alphacalcidol in Prevention of Glucocorticoid-Induced Osteoporosis

in Calcified Tissue International (1999), 65(4), 328-31

One of the major drawbacks of glucocorticoids long-term therapy is the occurrence of a severe osteoporosis characterized by fractures occurring at different sites, mainly at the level of trabecular bone ... [more ▼]

One of the major drawbacks of glucocorticoids long-term therapy is the occurrence of a severe osteoporosis characterized by fractures occurring at different sites, mainly at the level of trabecular bone. One of the major determinants of glucocorticoid-induced osteoporosis is a decrease in the intestinal absorption of calcium (Ca) leading to a secondary hyperparathyroidism. D-hormones have been shown to significantly improve Ca absorption in the gut and subsequently to decrease parathyroid hormone circulating levels, hence normalizing bone turnover. In a recent study evaluating 145 patients suffering from diseases requiring long-term treatment with high doses of corticosteroids, we have demonstrated a significant benefit of alphacalcidol (1 microg/day) over placebo in terms of changes in bone mineral density of the lumbar spine. These results are in accordance with studies showing better prevention of bone loss and vertebral fractures in cardiac transplant patients treated with alphacalcidol than those treated with etidronate. There is now a convergent body of evidence to suggest that alphacalcidol is a reasonable, safe, and effective option for the prevention of glucocorticoid-induced osteoporosis, provided that serum Ca is monitored on a regular basis. [less ▲]

Risedronate produces dose-dependent increases in bone mineral density in postmenopausal women with low bone mass

in Calcified Tissue International (1999), 64(S1), 69

Risedronate, a highly effective, short-term oral treatment for Paget’s disease: a dose-response study

in Calcified Tissue International (1999), 64

Limited clinical utility of a self-evaluating risk assessment scale for postmenopausal osteoporosis: lack of predictive value of lifestyle-related factors

in Calcified Tissue International (1999), 65(5), 354-358

The aim of this study was to assess the efficiency of a self-administered questionnaire to identify subjects with postmenopausal osteoporosis in the setting of first line medical care. A sample of 300 ... [more ▼]

The aim of this study was to assess the efficiency of a self-administered questionnaire to identify subjects with postmenopausal osteoporosis in the setting of first line medical care. A sample of 300 postmenopausal women completed the questionnaire based on 18 items. Bone mineral density at the lumbar spine (BMD-L), total hip (BMD-H), and femoral neck (BMD-N) was used as objective criterion for evaluation. The mean risk score was 8.2 +/- 3.21. BMD was correlated with total risk score: r = -0.32 for BMD-L, -0.36 for BMD-N, and -0.43 for BMD-H. Cutoff points for the risk score (equal likelihood points) according to a T-score threshold of -2.5 were 8.6 for BMD-L and BMD-N and 9.3 for BMD-H; specificity and sensitivity was 62% and 62%, respectively, for BMD-L, 65% and 62% for BMD-N, and 75% and 63% for BMD-H. Stepwise multiple regression analysis of the questionnaire items in relation to BMD showed higher correlation coefficients for models including individual items rather than the overall risk score. Items concerning low weight, older age, and wrist fracture after 50 years of age were always selected as significant determinants of BMD (R = 0.43-0.55). Hormonal replacement therapy was also an important determinant. Lifestyle-related items did not contribute significantly. In conclusion, the diagnostic performance of the 18-item self-administered questionnaire was poorer than a shortened questionnaire omitting lifestyle factors. The clinical utility of a questionnaire should ultimately be evaluated in the specific optic of a chosen global strategy for prevention of osteoporotic fractures. [less ▲]

Expression of Bone Sialoprotein in Human Lung Cancer

in Calcified Tissue International (1997), 61(3), 183-8

Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown ... [more ▼]

Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown. The recent demonstration that human breast cancer cells express and attach to bone sialoprotein (BSP), a sulfated phosphoprotein rich in bone and other mineralized tissues, could provide a clue to elucidating bone metastases formation. BSP contains the integrin binding peptide Arg-Gly-Asp (RGD), as well as non-RGD cell attachment domain. Using an immunoperoxidase technique and a specific polyclonal antibody directed against a BSP synthetic peptide, we examined the expression of BSP in 48 lung lesions including 25 squamous carcinoma, 21 adenocarcinoma, and 2 bronchioloalveolar cancers, as well as 38 human ovarian carcinoma that constitute a group of generally nonosteotropic cancers. BSP was not specifically detected in normal lung tissue with the exception of cartilage associated with bronchi. Most of the adenocarcinoma (74%) and all squamous carcinoma of the lung examined exhibited detectable levels of BSP. Staining was mainly cytoplasmic and membrane associated. The two bronchioloalveolar lung cancers examined did not show detectable amounts of BSP. When microcalcifications were observed in pulmonary malignant lesions, they were usually associated with cancer cells expressing BSP. Only 21% of the ovarian cancers examined contained malignant cells with 2+ or 3+ positivity for BSP. We further demonstrated that in 8 of 10 additional lung cancers, BSP was detected at the mRNA level. Our observation is the first demonstration that BSP is expressed in non-small cell lung carcinoma. Lung cancer cells are now the second type of osteotropic malignant cells described to express BSP. Added to the observation that BSP expression is not frequent in ovarian carcinoma, a low osteotropic cancer, our study supports our hypothesis that BSP could play a role in determining the affinity of cancer cells to bone. [less ▲]

Design for an Ipriflavone Multicenter European Fracture Study

in Calcified Tissue International (1997), 61(Suppl 1), 28-32

In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large ... [more ▼]

In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged > 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, double-blind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 x 200 mg/day of i.p. or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of i.p. in preventing vertebral nontraumatic fractures. Fracture is defined here as a > or = 20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with i.p. would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that i.p. significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women. [less ▲]

Comparative analysis of healthcare use in patients with rheumatoid arthritis and control subjects without chronic disease

in Calcified Tissue International (1997), 61

Direct social costs of Osteoporotice hip fractures in Belgium

in Calcified Tissue International (1997), 61

Harmonization of clinical practice guidelines for the prevention and treatment of osteoporosis and osteopenia in Europe : a difficult challenge

in Calcified Tissue International (1996), 59(S1), 24-29