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Biomedical subjects

B J Riis

Publications and source records attributed to B J Riis.

At least 19 recordsLinked to original sources
PubMed2006

Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?

OBJECTIVE: Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize emerging observations from the molecular level to the preliminary clinical findings of possible chondroprotective effects of calcitonin. METHOD: This review summarizes peer-reviewed articles found using pre-defined search criteria and published in the PubMed database before January 2006. In addition, abstracts from the OsteoArthritis Research Society International (OARSI) conferences in the time period 2000-2005 have been included in the search. RESULTS: Ample evidence for the effect of calcitonin on bone resorption was found. Support for direct effects of calcitonin on chondrocytes on matrix synthesis and inhibition of cartilage degradation have been published. In addition, clinical evidence for the effect of calcitonin on cartilage degradation is emerging. CONCLUSION: Several independent lines of evidence suggest a direct chondroprotective effect of calcitonin in addition to the well-established effect on bone resorption. Given the currently limited availability of chondroprotective agents, much expectation regards the ongoing clinical assessment of calcitonin therapy for the prevention and treatment of OA.

Animals↗
PubMed2003

Adverse effects of a SERM (Levormeloxifene). Safety parameters and bone mineral density 12 months after treatment withdrawal.

OBJECTIVE: Levormeloxifene is a selective estrogen receptor modulator (SERM). The development of the drug was discontinued due to intolerable adverse effects. This paper follow-up on the adverse events in a group of 234 women that was followed for 12 months without treatment after 12 months of treatment with levormeloxifene. METHODS: Adverse events were recorded at all clinical visits. The double-layer thickness of the uterine endometrium was determined by transvaginal ultrasonography. Endometrial biopsies were obtained by pipelle. The biopsies taken at the entrance to the follow-up phase were taken under hysteroscopy-guidance. Bone mineral density of the total body, lumbar spine (L1-L4), hip and forearm was measured by dual-energy X-ray absorptiometry. RESULTS: The most prominent adverse event was increased endometrial thickness over the pre-defined threshold of 8 mm. No cases of proliferative endometrium were reported. Following withdrawal of treatment the mean endometrial thickness approached baseline levels in a dose dependent manner. Hysteroscopic examinations showed that levormeloxifene was related to increased incidence of edema, vascularization and cysticity. In the levormeloxifene groups, a total of eight women had utero-vaginal prolapse and five women reported urinary incontinence (including worsening of a previously existing condition). Bone density in the spine and hip approached baseline levels during the 12 months of follow-up without treatment. CONCLUSION: Endometrial thickening, seen in association with the use of some SERM's, may lead to harmful adverse effects more than 12 months after treatment is initiated. Levormeloxifene prevents the postmenopausal bone loss, but the lowest effective dose is unknown.

Bone Density↗
PubMed2001

The effect of fluvastatin on parameters of bone remodeling.

Statins decrease the hepatic biosynthesis of cholesterol, and reduce the incidence of myocardial infarction in women who have already experienced a myocardial infarction. Statins also reduce the risk of atherosclerosis in diabetic patients, but it is unknown whether they influence the glucose tolerance. It has further been suggested that they may influence bone metabolism. Vitamin C is an antioxidant and it decreases serum cholesterol moderately. Antioxidants may also have other metabolic effects, but these are insufficiently studied. The aim of the present study was to investigate the metabolic effects of the cholesterol-lowering agent fluvastatin and the antioxidant vitamin C. Sixty-eight elderly, postmenopausal women with osteoporosis and mild hypercholesterolemia were randomly assigned to 12 weeks open treatment with either fluvastatin (40 mg daily) + 500 mg vitamin C (n = 45) or vitamin C only (n = 23). We measured biochemical markers of bone formation (serum osteocalcin and total alkaline phosphatase) and bone resorption (serum and urinary CTX), parameters related to diabetes and serum lipids and lipoproteins. Fluvastatin in combination with vitamin C had no effect on bone formation markers. We found a weak decrease in parameters of bone resorption, which was significant from baseline, but not different between the two groups. There were no significant effects on any of the other markers of either fluvastatin or vitamin C. The lipid-lowering effect of fluvastatin was confirmed with a decrease of 20% and 30% in serum total cholesterol and LDL-cholesterol, respectively. We conclude that fluvastatin given in clinically relevant doses has no influence on parameters of bone remodeling. Other statins remain to be investigated.

Aged↗
PubMed2001

Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy.

Three hundred and one healthy women between 45 and 65 yr of age and at least 1 yr postmenopausal were randomly assigned to 12-month double-blind therapy with levormeloxifene [1.25 (n = 51), 5, 10, or 20 mg/day], low dose continuous combined hormone replacement therapy [HRT; 1 mg 17 beta-estradiol and 0.5 mg norethisterone acetate/day], or placebo (all n = 50). All of the women were also given a daily supplement of calcium (500 mg). Serum CrossLaps decreased by about 50% in the levormeloxifene groups, with no dose-response effect. The group receiving HRT decreased more (>60%), and the placebo group (500 mg calcium alone) decreased by about 10%. The pattern was similar for bone alkaline phosphatase, except that the decreases were smaller, about 30% for the levormeloxifene groups and 50% for the HRT group. Serum osteocalcin also showed highly significant decreases, of the same magnitude in the levormeloxifene and HRT groups. Spinal bone mineral density (BMD) decreased by less than 1% in the placebo group and increased by about 2% in the levormeloxifene groups and by almost 5% in the HRT group (P < 0.001 for the difference between levormeloxifene and HRT vs. placebo). BMD of the total hip and total body changed in the same direction, although differences between groups were not as pronounced as those for BMD spine. Total cholesterol decreased by about 13--20% during levormeloxifene therapy, whereas daily doses of 1 mg estradiol and 0.5 mg norethisterone acetate produced a decrease of only about 8%. Levormeloxifene decreased low density lipoprotein cholesterol by about 22-30% compared with about 12% in the low dose HRT group. High density lipoprotein cholesterol was unchanged in all groups. Endometrial thickness increased both clinically and statistically significantly in the levormeloxifene groups independently of the dose; the difference from the placebo and HRT groups was significant (P < 0.001). There was no significant difference between the HRT and placebo groups. Other adverse events of interest include hot flushes, which did not occur more frequently in the levormeloxifene than the placebo groups, but occurred significantly less frequently in the HRT group (P < 0.05). Breast tenderness was much more common in the HRT group (<0.001) than in all other groups. In conclusion, the study shows that levormeloxifene, a new selective estrogen receptor modulator, has positive effects on BMD and bone turnover and apparently strong estrogenic effects on the serum concentrations of different cholesterol subfractions. Levormeloxifene at the doses tested had an estrogen-like effect on endometrium and no effect on hot flushes. The study was unable to differentiate between the effects of the different doses of levormeloxifene.

Bone Density↗
PubMed2001

Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis.

The objective of this study was to compare efficacy and safety of continuous versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55-75 years with postmenopausal osteoporosis were randomized to active treatment or placebo. Similar total doses of ibandronate were provided by treatment regimens with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg of ibandronate every other day for the first 24 days, followed by 9 weeks without active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12 months to receive either continuous (n = 37) or intermittent ibandronate (n = 35). By 24 months, bone mineral density (BMD) had increased significantly relative to baseline in both active treatment groups. The continuous and intermittent groups showed statistically equivalent increases in lumbar spine BMD of +5.64% (+/-0.53) and +5.54% (+/-0.53) and in total hip of +3.35% (+/-0.40) and +3.41% (+/-0.40), respectively (per protocol population). Biochemical markers of bone turnover decreased significantly in both treatment groups. The level of marker suppression was similar, although the intermittent group displayed, as expected, more fluctuation over the treatment period. The frequency of adverse events was similar in the treatment groups. In conclusion, the intermittent and continuous regimens showed equivalent changes in BMD and bone turnover. These results confirm previous preclinical findings indicating that the efficacy of ibandronate depends on the total oral dose given rather than on the dosing schedule. This supports development of new flexible dosing regimens targeted to minimize the frequency of dosing, which are expected to improve convenience and lead to enhanced long-term patient compliance.

Administration, Oral↗
PubMed1999

Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomized study.

Sodium fluoride stimulates bone formation and has been used to treat osteoporosis for decades despite debate about the antifracture efficacy. Hormone replacement therapy (HRT) results in only modest increases in bone mineral density (BMD). However, for women with low bone mass, the ideal therapy should not only inhibit bone resorption but simultaneously stimulate bone formation to increase bone mass above the fracture threshold. We thus performed a randomized, double-blind, placebo-controlled intervention study to prospectively investigate the effect of a low dose of fluoride, in combination with HRT, on BMD and biochemical markers of bone turnover. One hundred healthy postmenopausal women (60-70 yr old) were thus randomly assigned to: 1) HRT [transdermal 17beta-estradiol, releasing 50 microg/day; plus oral norethisterone acetate (NETA), 1 mg/day]; or 2) oral monofluorophosphate (MFP; equivalent to fluoride, 20 mg/day); or 3) HRT+MFP; or 4) placebo, for 96 weeks. All participants received a calcium supplement of 1000 mg/day. Sixty-eight women completed the study. We found a pronounced, linear increase in spinal BMD during treatment with HRT+MFP [11.8% (1.7% SEM)], which was significantly greater than the increase in the HRT group [4.0% (0.5% per yr); P < 0.05]. MFP produced a smaller increase [2.4% (0.6% per yr)], whereas there was no change in the placebo group [0.0% (0.5% SEM)]. Similar changes were found at the other skeletal sites (distal forearm, hip, and total body). Markers of bone formation showed a fall in the HRT group, which was significantly more pronounced than in the combined HRT+MFP group. A nonsignificant increase was found in the MFP group, whereas the placebo group showed a decrease caused by calcium treatment. The marker of bone resorption decreased significantly more in the HRT and the HRT+MFP groups than in the placebo group but tended to increase in the MFP group. In conclusion, this study shows, by use of biochemical markers of bone turnover, that bone resorption and formation may be dissociated, as a result of actions of two compounds with diverging effects on bone turnover. Furthermore, the synergistic effects of relatively low doses of the compounds suggested statistically and clinically significant increases in trabecular and probably also cortical bone. Adverse effects were relatively rare and mild.

Aged↗
PubMed1997

Design for an ipriflavone multicenter European fracture study.

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.

Absorptiometry, Photon↗
PubMed1996

Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study.

The aim of the study was to examine the role of peak bone mass and rate of postmenopausal bone loss for the subsequent risk of osteoporotic fracture. 182 women within 3 years of menopause were followed longitudinally for 15 years. Over the first 2 years, forearm bone mass (single photon absorptiometry) was measured nine times, the rate of bone loss was calculated, and the women were stratified into a group of "fast bone losers" (n = 49) and a group of "normal bone losers" (n = 133). Later, bone mass was also measured in the lumbar spine and hip with dual energy X-ray absorptiometry. At 15 years, the fast losers had significantly lower body weight (4.4 kG; p < 0.05) than the normal losers. Furthermore, the fast losers had significantly increased values of bone turnover (osteocalcin and C-terminal type I collagen breakdown products). In both the forearm, spine, and hip, the fast bone losers had at all sites significantly less bone mass than the normal bone losers (p < 0.001). 23 women had experienced a peripheral (Colles') fracture and 25 a spinal fracture. The fracture groups had generally significantly (p < 0.05) less bone mass than the group without fracture, both in the forearm, spine, and hip and they also had the highest rate of bone loss after menopause (p < 0.05). Baseline bone mass and rate of loss predisposed to the same extent to fractures with ODD's ratios of about 2. If both low bone mass and rate of loss were present, the ODD's ratio increased to about 3. We conclude that fast rate of bone loss and low bone mass are equally important for the risk of fracture. The identification of women at risk of osteoporosis should therefore consider both a measurement of bone mass status, and a determination of the postmenopausal rate of loss.

Bone Density↗
PubMed1996

The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study.

The present article describes the results from a phase II dose finding study of the effect of ibandronate, a new, third generation bisphosphonate, in postmenopausal osteoporosis. One hundred and eighty postmenopausal, white women, at least 10 years past a natural menopause, with osteopenia defined as a bone mineral density (BMD) in the distal forearm at least 1.5 SD below the premenopausal mean, entered and 141 (78%) completed a 12 months randomized, double-blind, placebo-controlled study. The women received 0.25, 0.5, 1.0, 2.5, or 5.0 mg ibandronate daily or placebo. All women received a daily calcium supplementation of 1000 mg Ca2+. Bone mass and biochemical markers of bone turnover were measured every 3 months throughout the study period. The average changes in bone mass showed positive outcome in all regions in the groups receiving ibandronate 2.5 and 5.0 mg. The responses in the two groups were not significantly different, although there was a tendency toward a higher response in bone mass in the group receiving ibandronate 2.5 mg, where the increase in BMD was 4.6 +/- 3.1% (SD) in the spine (p < 0.001), 1.3 +/- 3.0% (SD) to 3.5 +/- 5.3% (SD) in the different regions of the proximal femur (p < 0.03 to p < 0.002), and 2.0 +/- 1.9% (SD) in total body bone mineral content (BMC) (p < 0.001). There was no significant changes in bone mass in the group receiving calcium (placebo) and ibandronate 0.25 mg. Dose-related responses were found in all biochemical markers of bone turnover. In average, serum osteocalcin decreased 13 +/- 14% (SD) (placebo) and 35 +/- 14% (SD) (5.0 mg). Urinary excretions of breakdown products of type I collagen decreased 35 +/- 21% (SD) (placebo) and 78 +/- 28% (SD) (5.0 mg), p < 0.001 in all groups. In conclusion, the results suggest that ibandronate treatment increases bone mass in all skeletal regions in a dose dependent manner with 2.5 mg being the most effective dose. Ibandronate treatment reduces bone turnover to premenopausal levels and is well tolerated.

Absorptiometry, Photon↗
PubMed1995

The role of bone loss.

Our longitudinal studies of early postmenopausal women have shown that there are two characteristic groups. Approximately 35% lose significant amounts of bone mineral (the "fast losers"), whereas approximately 65% lose only a minor amount of bone mineral (the "normal losers"). The rate of bone loss in postmenopausal women may be indirectly assessed by use of a number of biochemical markers. New markers have recently been developed, i.e., more specific and robust markers of both bone resorption and formation. The urinary concentration of degradation products of type I collagen and osteocalcin assays that are stable in serum may optimize the procedure to assess the rate of loss. We and others have shown that these markers correlate to the rate of bone loss with fairly high r values. A prospective 12-year study revealed that the fast bone losers still had significantly higher bone turnover than the normal bone losers. The role of baseline bone mass and rate of loss on fracture risk was evaluated. The data showed that a low baseline bone mass (below -1 SD) and a fast rate of loss predisposed to fracture to the same extent with an odds ratio of approximately 2. A combination of a low baseline bone mass and a fast rate of loss increased the odds ratio of having a fracture. In conclusion, these data suggest that a low bone mass and a fast rate of bone loss play equal roles for the future risk of fracture.

Biomarkers↗
PubMed1995

Single X-ray absorptiometry: performance characteristics and comparison with single photon absorptiometry.

The aim of the present study was to evaluate a new device for measurement of forearm bone mass using the technique of single X-ray absorptiometry (SXA, DTX-100; Osteometer A/S, Rødovre, Denmark), and to compare the performance with the more traditional single photon absorptiometry (SPA, DT 100; Osteometer A/S, Rødovre, Denmark). The SPA phantom measurements showed a coefficient of variation of 0.43% and 0.42% for bone mineral content (BMC) and bone mineral density (BMD), respectively (39 months including seven source changes). The SXA precision errors were slightly lower with values of 0.30% and 0.30%, respectively. The patient measurements showed SPA coefficients of variation of 0.85% and 0.99% (BMC and BMD) and SXA coefficients of variation of 0.56% and 0.83%, respectively. The correlation between SPA and SXA values performed in 377 individuals yielded r values of 0.99 and 0.98 for BMC and BMD, respectively. The correlations between SXA measurements of the dominant and non-dominant forearm yielded an r-value of 0.95, with a slope of 0.949 (p < 0.001) and an intercept of 0.204 (p < 0.05). The non-dominant forearm thus had approximately 3% lower BMC than the dominant (the same was true for BMD). Correlations to spine and femur ranged from r = 0.48 to r = 0.75. In conclusion, the new single X-ray absorptiometry forearm bone densitometer described in this paper has performance characteristics which allows it to be used both for diagnostic purposes and for the follow-up of treatment.

Absorptiometry, Photon↗
PubMed1995

Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy.

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, and is therefore increasingly prescribed to prevent the development of postmenopausal osteoporosis. Because of individual differences in the response to HRT as well as problems with compliance, it has been debated how the skeletal response to HRT should be monitored. When estrogen production decreases at the menopause, a number of biochemical markers of bone turnover increase considerably in the order of 50%-100% from baseline. When HRT is instituted, the markers decrease again within the following 3-6 months. In the present prospective study we investigated whether the determination of biochemical markers of bone turnover may be useful for monitoring the skeletal effect of HRT. Seventy-six early postmenopausal women received HRT and 43 received placebo. The treatment period was 24 months and the women were followed with repeated bone mass measurements (every 3 months) which allowed calculation of the bone loss. Serum and urine samples were collected at 3, 6, 12 and 24 months. The placebo group lost a significant amount of bone mineral density in both the forearm and the spine (p < 0.001), whereas the HRT group did not. There was, however, a relatively large overlap of values between the HRT and placebo groups, especially in the spine. After 3 months' treatment the correlation between the changes in the markers and the bone loss was r = 0.59, and this value increased to r = 0.66 at 6 months and r = 0.76 and r = 0.77 at 12 and 24 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1995

Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment.

An enzyme-linked immunosorbent immunoassay (ELISA) for a new marker of bone resorption (CrossLaps) was evaluated. The ELISA procedure determines degradation products of type I collagen in urine. Values obtained in the ELISA and in pyridinoline by high pressure liquid chromatography were correlated after a correction for creatinine. A high correlation was found (r = 0.77; n = 81). A group of postmenopausal women (n = 180) showed an increase of more than 70% compared to values in premenopausal women (n = 104). Hydroxyproline was increased by 23%, osteocalcin by 52%, pyridinoline by 31%, and deoxypyridinoline by 50%. A highly significant decrease (60.7%) in the CrossLaps values was seen after 12 months in samples from patients receiving hormone replacement therapy compared to a placebo group. The spontaneous bone loss in an untreated group of women was determined by repeated forearm bone mass measurement over 24 months. Baseline values obtained in the CrossLaps ELISA were correlated to the rate of loss, yielding a highly significant r value of -0.61, indicating that CrossLaps might be a useful parameter for assessment of the risk of osteoporosis in postmenopausal women.

Amino Acid Sequence↗
PubMed1995

The effect of menopause and hormone replacement therapy on bone alkaline phosphatase.

We evaluated two different assays for the determination of bone-specific alkaline phosphatase (B-AP). One assay was a direct method using a two-site IRMA (AP(Hyb)). The other assay determined B-AP indirectly after precipitation with lectin (AP(BM)). The assays were compared to serum osteocalcin (levels) and total AP in 20 premenopausal women and in 40 early postmenopausal women before and after 9 months of treatment with hormone replacement therapy (HRT) (n = 20) or placebo (n = 20). Serum osteocalcin correlated with serum AP(Hyb) (r = 0.45), and with serum AP(BM) (r = 0.33) (both p < 0.001). The correlation between AP(Hyb) and AP(BM) was moderate, r = 0.71 (p < 0.001). When comparing postmenopausal to premenopausal women, serum osteocalcin had a t score (mean +/- SEM) of 2.30 +/- 0.29 followed by total AP(T-AP) (1.20 +/- 0.28), AP(Hyb) (1.05 +/- 0.33) and AP(BM) (0.64 +/- 0.21) (paired t-test: p < 0.01 for osteocalcin vs. other markers). After 9 months of HRT all markers had declined significantly to premenopausal levels (mean +/- SEM): osteocalcin with 44.5% +/- 6.1%; AP(BM) with 32.1% +/- 5.6%; AP(Hyb) with 36.4% +/- 4.4% and T-AP with 24.4% +/- 2.9%; p < 0.001. Of the markers, only serum osteocalcin correlated significantly with the rate of bone loss in the placebo group (r = 0.52, p < 0.02). We conclude that both assays for B-AP reflect bone turnover in postmenopausal women with and without HRT. Under controlled conditions they did not show any advantage of osteocalcin in diagnosing increased bone turnover or monitoring the effect of an anti-resorptive therapy in postmenopausal women.

Adult↗