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Biomedical subjects

C Christiansen

Publications and source records attributed to C Christiansen.

At least 55 records · Page 3Linked to original sources
PubMed2003

Does serum cholesterol contribute to vertebral bone loss in postmenopausal women?

Recent in vitro and animal studies suggest that cholesterol and its metabolites inhibit the functional activity of osteoblasts and thereby induce reduced bone mineralization. However, scant information is available on the clinical implication of these findings with special regard to postmenopausal bone loss. Therefore, the aim of the present study was to investigate cross-sectional and longitudinal associations between serum cholesterol, bone mineral density (BMD), and bone turnover in 340 postmenopausal women aged 50-75 years (mean 59 years), who were followed for 8.3 +/- 1.1 years. BMD in the lumbar spine, distal forearm, and total hip was measured by dual energy X-ray absorptiometry. Other study variables were physical measures, serum cholesterol, serum markers of bone turnover, and self-reported information on various risk factors for osteoporosis. At baseline, serum cholesterol showed significant negative correlation with BMD at the lumbar spine (r = -0.21, P < 0.0001) and distal forearm (r = -0.14, P = 0.013), but not at the hip. No associations of serum cholesterol with serum osteocalcin (r = 0.054, P = 0.317) and CTX (r = -0.027, P = 0.623) were, however, noted. After adjustment for age and BMI, the negative correlation remained significant at the lumbar spine (r = -0.16, P = 0.004), but not at the distal forearm (r = -0.018, P = 0.738). At the end of the 8-year follow-up, the correlation between serum cholesterol and spine BMD was not observed. Those with the largest increases in serum cholesterol, however, showed the greatest decreases in spine BMD independently of the changes in BMI (r = -0.16, P = 0.004). The correlation between the changes in serum cholesterol and the simultaneous changes in osteocalcin (r = 0.081, P = 0.140) and CTX (r = 0.042, P = 0.441) were statistically insignificant. Thus, our results suggest that the weak associations between spine BMD and serum cholesterol can be explained by the fact that both variables are simultaneously affected by estrogen deficiency rather than by a direct influence of serum cholesterol on osteoblast function.

Aged↗
PubMed2003

The efficacy of 48-week oral ibandronate treatment in postmenopausal osteoporosis when taken 30 versus 60 minutes before breakfast.

Since effective prevention and treatment of osteoporosis demands a high degree of long-term compliance, optimization of the dosing regimen in terms of efficacy and convenience of drug intake is a critical issue of oral bisphosphonate treatment. The purpose of the present study was to investigate whether the efficacy of the treatment with oral ibandronate, 2.5 mg daily, can be maintained if changing the postdose fast from 60 to 30 min. This was a 48-week, multicenter, open-label, randomized, parallel-group noninferiority study. Subjects were postmenopausal women 55-80 years old with lumbar spine (L1-L4) bone mineral density (BMD) corresponding to a T score < or =2.5. Women were randomly assigned to take 2.5 mg ibandronate exactly 30 or 60 min before breakfast. Lumbar spine and proximal femur (trochanter, femoral neck, total hip) BMD were measured by dual energy X-ray absorptiometry; serum osteocalcin and creatinine-corrected urinary C-telopeptide of type I collagen (u-CTX/Cr) excretion were measured by ELISA. After 48 weeks of treatment, the relative increase in lumbar spine BMD from baseline in the 30-min fast group was lower than that in the 60-min fast group (3.07% versus 4.95%, one-sided 97.5% CI = -2.89%) such that the prespecified noninferiority criteria were not met. The mean relative increases in BMD at the trochanter (3.04% versus 4.36%), femoral neck (1.82% versus 2.19%), and total hip (2.35% versus 3.21%) in the 30-min fast group were also lower than those in the 60-min fast group. Less suppression of the markers of bone turnover (u-CTX/Cr, -48.5% vs -61.8%; serum osteocalcin, -34.8% vs 43.8%) was observed in the 30-min compared with the 60-min group. In conclusion, if reducing the postdose fasting interval, dose-increase compensation would likely to be required to maintain efficacy of oral ibandronate treatment. Another potential solution for improving the convenience with bisphosphonate treatment is expected from weekly or monthly dosing regimens currently under clinical investigations.

Absorptiometry, Photon↗
PubMed2003

Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens.

The aims of the present study were to investigate how changes in the cumulative dose and the frequency of dosing influence the short-term antiresorptive efficacy of oral ibandronate treatment and whether serial measurements of bone markers could provide a useful diagnostic tool for the revelation of noncompliance to established treatments with antiresorptive drugs. Study participants were 200 healthy women 50-70 years old (mean 63.1 years) with a lumbar spine BMD t-score of -1 to -5. Women were randomly allocated to receive treatment with oral ibandronate according to one of the following eight dosing regimes: (1) 2.5 mg daily for 84 days; (2) 20 mg weekly for 84 days; (3) 2.5 mg daily for 28 days + no treatment for 56 days; (4) 2.5 mg daily for 28 days + 2.5 mg weekly for 56 days; (5) 2.5 mg daily for 28 days + 2.5 mg three times weekly for 56 days; (6) 2.5 mg daily for 14 days + 2.5 mg three times weekly for 56 days; (7) 2.5 mg three times weekly for 84 days; (8) no treatment for 168 days. Study parameters were the serum concentration of the C-terminal telopeptide of collagen type I (s-CTX, resorption marker) and N-MID osteocalcin (formation marker) measured by enzyme-linked immunosorbent assay. Oral treatment with ibandronate 20 mg weekly (cumulative dose 240 mg) resulted in greater final inhibition in s-CTX and area under the curve (AUC) compared to the 2.5 mg daily treatment (cumulative dose 210 mg), indicating that as long as optimal doses are administered the frequency of dosing has secondary importance for overall efficacy. When the cumulative dose was 130 mg or less, the final degree of inhibition was still the function of the cumulative dose, but the overall efficacy estimated by the AUC was also under the influence of the frequency of dosing. These observations suggest that serial measurements of s-CTX may provide a useful diagnostic tool for the early revelation of suboptimal dosing or noncompliance to already optimized therapies with antiresorptive agents.

Administration, Oral↗
PubMed2003

Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis.

Short-term changes in biochemical markers of bone turnover (bone markers) have been suggested as predictors of long-term response in bone mass during antiresorptive treatment. In the Danish cohort (n = 306) of the Early Postmenopausal Intervention Cohort (EPIC) Study (n = 1609) of oral alendronate (ALN) for prevention of postmenopausal osteoporosis, bone markers (urine C-telopeptides of type I collagen (uCTX), urine N-telopeptide cross-links of type I collagen (uNTX), serum total osteocalcin measured by ELISA [total OC (ELISA)], and serum total osteocalcin measured by RIA [total OC (RIA)]) were measured at 6-month intervals. The correlation between 6-month change in uCTX and 4-year change in spine and hip bone mineral density (BMD) was r = -0.41 and r = -0.42, respectively (P < 0.001). The corresponding values for the other bone markers were r = -0.53 and r = -0.42 (uNTX), r = -0.46 and r = -0.47 [total OC (ELISA)], and r = -0.43 and r = -0.41 [total OC (RIA)], all P < 0.001. ROC curves were used to analyse the ability of the bone markers to predict a change in spine BMD greater than 0%. The best performance [defined as the maximum value of (sensitivity plus specificity)] was found at the cut-off values of a -29% change from baseline in uCTX, a -45% change from baseline in uNTX, a -13% change from baseline in total OC (ELISA), and a -15% change from baseline in total OC (RIA). At these values the corresponding sensitivity was 66% (uCTX), 76% (uNTX), 70% [total OC (ELISA)], and 83% [total OC (RIA)]. The specificity was 80% (uCTX), 75% (uNTX), 71% [total OC (ELISA)], and 55% [total OC (RIA)]. The positive predictive value (PPV) was 82% (uCTX), 80% (uNTX), 77% [total OC (ELISA)], and 71% [total OC (RIA)]. The negative predictive value (NPV) was 64% (uCTX), 70% (uNTX), 64% [total OC (ELISA)], and 71% [total OC (RIA)]. In conclusion, the bone markers predicted a change in spine BMD greater than 0% with a high PPV and specificity. There was a trend toward better performance in this respect for the bone resorption markers.

Alendronate↗
PubMed2003

Oral weekly ibandronate prevents bone loss in postmenopausal women.

OBJECTIVES: To investigate the efficacy, safety, and dose-response of once-weekly oral ibandronate in the prevention of postmenopausal bone loss. DESIGN: This was a multi-centre, placebo-controlled, double-blind, randomized, 24-month phase II/III dose-finding study. SETTING: Primary care units in 14 osteoporosis centres. SUBJECTS: A total of 630 women were stratified into four strata according to time since menopause (TSM, 1-3 vs. >3 years) and baseline bone mineral density (BMD; normal: T-score > or =1 vs. osteopenic: -2.5 < or = T-score < or = 1) of the lumbar spine. INTERVENTIONS: Within each stratum women were further randomized to receive once-weekly ibandronate (5, 10, or 20 mg week-1) or placebo for 24 months. MAIN OUTCOME MEASURES: Efficacy parameters were the relative changes from baseline in spine (L1-4) and hip BMD, and biochemical markers of bone turnover (serum and urinary C-telopeptide of collagen type I (CTx), osteocalcin, and alkaline phosphatase) measured by dual energy X-ray absorptiometry and enzyme immunoassays, respectively. RESULTS: Once-weekly therapy with ibandronate induced dose-dependent increases in spine and hip BMD. At month 24, differences between the relative changes in spine and hip BMD induced by 20 mg ibandronate and placebo was 4.0 and 2.7%, respectively. Similar or more pronounced differences were seen in osteopenic women of TSM 1-3 years (5.3 and 3.5%) and of TSM >3 years (3.5 and 2.9%), respectively. A dose-dependent suppression of all biochemical markers of bone turnover was observed with significant decreases in the 20 mg dose groups of all strata at month 24. The overall safety results indicated that once-weekly oral ibandronate was well-tolerated at all three doses. CONCLUSION: Once-weekly oral therapy with 20 mg ibandronate provides an effective and safe therapy for the prevention of postmenopausal bone loss.

Administration, Oral↗
PubMed2003

Associated response in bone mineral density and atherogenic lipid profile during treatment with two different selective estrogen receptor modulators: levormeloxifene and raloxifene.

OBJECTIVE: We recently demonstrated a correlation between the responses in two target areas, bone and lipids, during treatment with hormone replacement therapy. Whether the same association exists during treatment with selective estrogen receptor modulators (SERMs) has not been examined before. STUDY DESIGN: This was an exploratory, post hoc analysis of data from two randomized, double-blind, placebo-controlled trials. STUDY POPULATION: From both studies we examined only the Danish subpopulation. Study 1 included 133 women treated with placebo or levormeloxifene in four different doses for 12 months, and study 2 included 248 women treated with raloxifene in three different doses or placebo for 24 months. MEASUREMENTS: Bone mineral density (BMD) of the spine and hip was measured semiannually. Serum lipids and biochemical bone markers were determined at each visit. To eliminate interindividual differences, all values were calculated as individual percentage change from baseline. RESULTS: We found a significant correlation between the increase in BMD of the spine and hip and the decrease in total cholesterol and low-density lipoprotein. CONCLUSION: Our study showed that, in healthy postmenopausal women, the women with the greatest response in BMD were also those with the most favorable response in lipid profile during treatment with SERMs.

Aged↗
PubMed2003

Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index.

BACKGROUND: Cartilage normally has a slow turnover but in arthritis increased metabolism results in degradation of the tissue. OBJECTIVE: To assess cartilage turnover in a sample of the general population by an assay measuring cartilage derived urinary collagen type II (CTX-II) C-telopeptide degradation products. METHODS: CTX-II concentrations were measured in urine samples from 615 healthy men and women aged 20-87 years, and the influence of age, sex, menopause, hormone replacement therapy (HRT), and body mass index (BMI) was assessed. RESULTS: CTX-II concentrations showed age dependent variations, with notable differences between men and women. Mean (SD) CTX-II concentration in postmenopausal women (220 (118) ng/mmol, n=25) was significantly higher than in an age matched group of premenopausal women (112 (79) ng/mmol, n=26, p<0.001). CTX-II concentration in women using HRT (118 (57) ng/mmol, n=50) was significantly lower than in an age and BMI matched group of women not receiving HRT (215 (99) ng/mmol, n=50, p<0.001). In subjects with a BMI >or=25 kg/m(2), CTX-II concentrations were significantly higher than in those with a BMI <25 kg/m(2) (185 (114) v 148 (91) ng/mmol, p<0.001). CONCLUSIONS: Cartilage turnover, as assessed by measuring urinary degradation products of CTX-II varies considerably with age, and significant differences between CTX-II levels in men and women as well as in pre- and postmenopausal women are found. Further studies are required to validate the marker for assessing cartilage degradation in arthritis.

Adult↗
PubMed2002

Investigation of bone disease using isomerized and racemized fragments of type I collagen.

In the collagen type I C-telopeptide an aspartyl-glycine site within the sequence AHDGGR is susceptible to molecular rearrangement. In newly synthesized collagen this site is in the native form, denoted alpha L. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (beta L) a racemized form (alpha D), and an isomerized/racemized form (beta D). In this study, we measured the urinary excretion of the four forms of C-telopeptides (CTX) in healthy adults and in patients with bone diseases. Levels of all CTX forms were higher in healthy postmenopausal women (P<0.001) compared with premenopausal controls. Levels decreased within 3 days of bisphosphonate treatment indicating that all CTX forms reflect bone resorption. In hyperthyroidism, characterized by a generalized increased bone turnover, native (alpha L) and age-modified (beta L, alpha D and beta D) forms increased to a similar extent compared to controls, resulting in normal ratios between the alpha L and age-modified forms of CTX. Conversely, in Paget's disease and prostate cancer-induced bone metastases, conditions characterized by focal increased bone turnover, alpha L CTX levels were more elevated than those of age-related CTX forms, resulting in increased ratios between native and age-modified CTX. For example, the ratio alpha L/alpha D was increased 7-fold in Paget's disease (P<0.001) and 2-fold in prostate cancer-induced bone metastases (P<0.002). In conclusion, the study suggests that in conditions with a localized alteration in bone turnover the ratio between alpha L CTX and the age-modified forms is significantly elevated. This may provide a new diagnostic and monitoring tool for diseases such as metastatic bone cancer and Paget's disease.

Adult↗
PubMed2002

Evidence of collective charge behavior in the insulating state of ultrathin films of superconducting metals.

Nonlinear I-V characteristics have been observed in insulating quench-condensed films which are locally superconducting. We suggest an interpretation in terms of the enhancement of conduction by the depinning of a Cooper pair charge density wave, Cooper pair crystal, or Cooper pair glass that may characterize this insulating regime. We propose that this is a more likely description than the Coulomb blockade or charge-anticharge unbinding phenomena.

Journal Article↗
PubMed2002

Changes in bone mineral density with age in men and women: a longitudinal study.

We performed a prospective study to evaluate the normal changes in bone mineral density (BMD) in the forearm, hip, spine and total body, and to study the agreement between changes in BMD estimated from cross-sectional data and the actual longitudinal changes. Six hundred and twenty subjects (398 women, 222 men; age 20-89 years) without diseases or medication known to affect bone metabolism undertook baseline evaluations, and 525 (336 women, 189 men) completed the study. BMD was measured twice 2 years apart by dual-energy X-ray absorptiometry. From cross-sectional evaluations the only premenopausal bone loss (<0.003 g/cm2/year) was found in the hip. In women after menopause and in men an age-related bone loss (0.002-0.006 g/cm2/year) was found at all sites. The data from the longitudinal evaluation showed a small bone loss in women before menopause at the hip and lumbar spine (<0.4%/year (<0.004 g/cm2/year)); this bone loss nearly tripled in the early postmenopausal years (<10 years since menopause), and thereafter decreased to the premenopausal rate for the hip, and to zero for the lumbar spine. The most pronounced bone loss after menopause occurred in the forearm (1.2%/year (0.006 g/ cm2/year)), and it remained constant throughout life. In men there was a small longitudinal bone loss in the hip throughout life, and a small bone loss in the distal forearm after the age of 50 years. In all groups, except for the early postmenopausal women, we found a small increase in total body BMD with age. When comparing the changes in BMD estimated from cross-sectional data with the longitudinal changes, only the hip and forearm generally displayed agreement, whereas the changes in the total body and spine generally were incongruous. In conclusion, the hip and forearm appear to be the sites with the best agreement between the cross-sectional estimated and the longitudinal age-related changes in BMD.

Adult↗
PubMed2002

Mechanism of circadian variation in bone resorption.

The diurnal variation in bone resorption markers is poorly understood and may contain essential information about regulation of bone resorption. To explore the acute regulation of bone resorption we studied bone turnover in 14 postmenopausal women during a randomized, crossover, 24 h study of oral glucose tolerance test (OGTT), normal diet, or fasting. Whereas fasting counteracted variation in bone resorption, as measured by serum C-telopeptide fragments of collagen type 1 degradation (s-CTx), OGTT and normal diet induced a 50% reduction (p < 0.001) over 2 h. For OGTT, s-CTx reverted to baseline levels after 6 h, and for normal diet s-CTx remained suppressed during the afternoon and returned to baseline overnight. Repeated OGTT at 8:00 A.M. and 8:00 P.M. in nine postmenopausal women demonstrated that identical reductions in s-CTx could be obtained at both timepoints with an intermediate return to baseline between tests. A 2 h randomized, crossover study of OGTT and fasting in 23 men and premenopausal women similarly revealed a 50% decrease in s-CTx. A randomized, crossover 2 h study of insulin tolerance test compared with fasting in six men and premenopausal women demonstrated a 20%-30% decrease in s-CTx (p < 0.01-0.05). Nine hour follow-up of ten healthy individuals during a crossover experiment of OGTT, protein, and fat intake revealed a comparable 50% reduction in s-CTx, but distinct profiles of serum glucose and serum insulin. Bone resorption was reduced by intake of food, glucose, fat, and protein and counteracted by fasting, and this seems to have been be independent of age and gender. Both exogenous and endogenous insulin stimulation tests induced a reduction in bone resorption, but this was only partial when compared with the reduction observed during food intake.

Biomarkers↗
PubMed2002

Association between pharmacokinetics of oral ibandronate and clinical response in bone mass and bone turnover in women with postmenopausal osteoporosis.

Data from the 1-year, phase II trial of oral ibandronate for treatment of postmenopausal osteoporosis are presented (n = 180). Participants were at least 10 years past menopause and had osteopenia defined as a forearm bone mineral density at least 1.5 SD below the premenopausal mean value. Doses were 0.25, 0.50, 1.0, 2.5, or 5.0 mg daily oral ibandronate or placebo. A total of 116 women treated with ibandronate completed the study. Blood samples for pharmacokinetic analyses were drawn 20 min, 40 min, 60 min, 2 h, 4 h, and 6 h after the first and last administration of the study drug. An enzyme-linked immunosorbent assay was used to determine the concentration of ibandronic acid (BM 21.0955) in serum (Enzymun-Test System ES 600). The assay is based on streptavidine technology to fix the capture antibody to the wall of the tube. Standards were prepared for each participant using individual drug-free serum. The serum concentration-time curves of ibandronate, expressed as the area under the curve over the sampling period (AUC(0-6h)), revealed a highly significant dose-response relationship, p < 0.0001, and linear pharmacokinetic behavior. An initial half-life (T(1/2lambda1)) in serum representing distribution and early elimination was 1.3 hours. Steady-state AUC (AUC(0-6h ss)) increased by a factor of 2.5, which is consistent with an apparent elimination half-life of 32.6 h and a dosing interval of 24 h. There was an exponential association between AUC(0-6h) (ss) and the change from baseline at month 12 in the bone markers (n = 116): r = -0.37 (serum total osteocalcin), r = -0.65 (urine C-telopeptides of type I collagen), and r = -0.65 (serum C-telopeptides of type I collagen), all p < 0.0001. All bone markers were maximally depressed at values of AUC(0-6h ss) of about 3 ng h/mL. AUC(0-6h ss) furthermore revealed a logarithmic association with change from baseline at month 12 in spine BMD, r = 0.39, p < 0.0001. In conclusion, the serum concentration of ibandronate was determined validly by the enzyme-linked immunosorbent assay. The data are the first to show highly significant associations between pharmacokinetic parameters of a bisphosphonate and the clinical response in bone mass and bone turnover.

Aged↗
PubMed2002

Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent.

In this study we examine the influence of number of years since menopause on spontaneous bone loss and response to hormone replacement therapy (HRT) in 274 women (56.1 +/- 4.2 years) completing two placebo-controlled HRT studies of 2 or 3 year duration. Both cross sectionally and longitudinally, bone loss in untreated women was greatest closest to menopause and declined thereafter (r = 0.34, p < 0.01 for lumbar spine bone loss and r = 0.25, p < 0.05 for femoral neck bone loss when correlated with number of years since menopause), such that the loss was eliminated in the femoral neck and bone mass increased in the spine in women >10 years after menopause. In contrast, bone turnover was consistently elevated throughout postmenopause, both cross-sectionally and longitudinally. The association with number of years since menopause was counteracted by both 1 and 2 mg estradiol combined with gestodene, piperazine, estrone sulfate in combination with norethisterone, and a combination of 2 mg estradiol and 1 mg norethisterone acetate. In addition, the response to various HRT regimens was independent of baseline bone mass. Whereas bone loss was significantly related to number of years since menopause, all HRT regimens applied arrested bone loss in healthy postmenopausal women, regardless of number of years since menopause.

Age Factors↗
PubMed2002

Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting.

We examined the diurnal variation in serum concentration of C-terminal telopeptide of type I collagen (serum CrossLaps, sCTx) under various conditions. The studies included a total of 100 individuals. Blood samples were collected every 3 h over 27 h. sCTx levels varied over the 24 h with a maximum at about 05:00 in the morning and a minimum of about 14:00 in the afternoon. The variation had a magnitude of about +/-40% around the 24 h mean and was similar in premenopausal and early and late postmenopausal women with normal and low bone mass. Furthermore, it was not affected by 5 days of bed-rest, by absence of a normal diurnal variation in cortisol production, or by absence of a normal light cycle (blindness). Nasal salmon calcitonin, an antiresorptive drug used for treatment of osteoporosis, was not able to break the circadian pattern whether the treatment was administered in the morning or the evening. The only parameter that showed a pronounced influence on the circadian variation was fasting, which reduced the variation significantly to about one fourth. From a practical point of view the results of this study demonstrate that samples for sCTx should be taken in the fasting state.

Adult↗
PubMed2002

Measurement precision and normal range of endometrial thickness in a postmenopausal population by transvaginal ultrasound.

OBJECTIVES: The aim of this study was to examine the endometrial thickness (ET) in an asymptomatic postmenopausal population, and to assess the long-term variability. DESIGN: A total of 1182 asymptomatic generally healthy postmenopausal women were enrolled into this cross-sectional evaluation of the ET. Measurements were performed by transvaginal ultrasound. A subset of the women (n = 178) was examined twice 3 months to 2 years apart to assess the long-term variability. RESULTS: Cross-sectionally, ET varied with length of menopause. During the first 5 years after menopause (YSM) the mean ET was 2.3 mm but it decreased by 0.03 mm/year (P < 0.01). From 5 to 13 YSM the ET remained stable at a mean of 1.8 mm with no significant changes (P = 0.13). Thereafter there was a minimal increase of 0.01 mm/year (P < 0.05). In order to minimize the influence of natural changes on ET, only women who had reached the menopause more than 5 years earlier were entered into the subsequent long-term study. The mean ET was 2.0 mm +/- 1.0 mm with no significant differences within or between the observers' measurements. The precision errors were less than 1 mm. CONCLUSIONS: The normal range of the thickness of the postmenopausal endometrium in asymptomatic women varies with YSM. There is a high long-term agreement within and between observers in measuring the ET.

Adult↗
PubMed2002

Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products.

BACKGROUND: Animal studies of arthritis have suggested that bisphosphonates may have chondroprotective abilities. OBJECTIVE: To evaluate the effect of bisphosphonate treatment on cartilage degradation. METHODS: Type II collagen is almost exclusively localised in cartilage, where it is the major structural component of the tissue. Hence fragments derived from this protein should represent a specific index for cartilage degradation. The urinary concentration of collagen type II C-telopeptide degradation products (CTX-II) was measured by a new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum concentration of collagen type I C-telopeptide degradation products (CTX-I), a marker of bone degradation, was also measured by ELISA. PARTICIPANTS: Two groups were studied. The alendronate group included 63 healthy postmenopausal women aged 45-54 randomly allocated to receive three years' treatment with 1 mg, 5 mg, 10 mg, or 20 mg alendronate daily or placebo. In the third year the women receiving 20 mg were switched to placebo. The ibandronate group included 119 women at least 10 years after the menopause aged <75 randomly allocated to receive 12 months' treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or placebo followed by 12 months without treatment. RESULTS: 20 mg of alendronate and 2.5 and 5 mg of ibandronate treatment produced significant decreases in urinary CTX-II to about 50% of baseline. The level reached after three months of treatment remained practically constant during the following 12-36 treatment months. When treatment was withdrawn CTX-II values returned towards baseline. Serum CTX-I also decreased rapidly within three months, but to a level of about 30% of baseline. CONCLUSIONS: The urinary excretion of CTX-II, a new marker of cartilage degradation, decreases significantly in response to bisphosphonate. This suggests that bisphosphonates may have chondroprotective effects in humans. By measurement of CTX-II it should be possible to monitor the effects of drugs that potentially inhibit cartilage destruction.

Alendronate↗
PubMed2001

Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial.

CONTEXT: Data on the efficacy and safety of ipriflavone for prevention of postmenopausal bone loss are conflicting. OBJECTIVES: To investigate the effect of oral ipriflavone on prevention of postmenopausal bone loss and to assess the safety profile of long-term treatment with ipriflavone in postmenopausal osteoporotic women. DESIGN AND SETTING: Prospective, randomized, double-blind, placebo-controlled, 4-year study conducted in 4 centers in Belgium, Denmark, and Italy from August 1994 to July 1998. PARTICIPANTS: Four hundred seventy-four postmenopausal white women, aged 45 to 75 years, with bone mineral densities (BMDs) of less than 0.86 g/cm(2). INTERVENTIONS: Patients were randomly assigned to receive ipriflavone, 200 mg 3 times per day (n = 234), or placebo (n = 240); all received 500 mg/d of calcium. MAIN OUTCOME MEASURES: Efficacy measures included spine, hip, and forearm BMD and biochemical markers of bone resorption (urinary hydroxyproline corrected for creatinine and urinary CrossLaps [Osteometer Biotech, Herlev, Denmark] corrected for creatinine), assessed every 6 months. Laboratory safety measures and adverse events were recorded every 3 months. RESULTS: Based on intent-to-treat analysis, after 36 months of treatment, the annual percentage change from baseline in BMD of the lumbar spine for ipriflavone vs placebo (0.1% [95% confidence interval (CI), -7.9% to 8.1%] vs 0.8% [95% CI, -9.1% to 10.7%]; P =.14), or in any of the other sites measured, did not differ significantly between groups. The response in biochemical markers was also similar between groups (eg, for hydroxyproline corrected for creatinine, 20.13 mg/g [95% CI, 18.85-21.41 mg/g] vs 20.67 mg/g [95% CI, 19.41-21.92 mg/g]; P =.96); urinary CrossLaps corrected for creatinine, 268 mg/mol (95% CI, 249-288 mg/mol) vs 268 mg/mol (95% CI, 254-282 mg/mol); P =.81. The number of women with new vertebral fracture was identical or nearly so in the 2 groups at all time points. Lymphocyte concentrations decreased significantly (500/microL (0.5 x 10(9)/L]) in women treated with ipriflavone. Thirty-one women (13.2%) in the ipriflavone group developed subclinical lymphocytopenia, of whom 29 developed it during ipriflavone treatment. Of these, 15 (52%) of 29 had recovered spontaneously by 1 year and 22 (81%) of 29 by 2 years. CONCLUSIONS: Our data indicate that ipriflavone does not prevent bone loss or affect biochemical markers of bone metabolism. Additionally, ipriflavone induces lymphocytopenia in a significant number of women.

Aged↗