Comparison of biochemical markers of bone remodelling in the assessment of the effects of alendronate on bone in postmenopausal osteoporosis.

The effects of alendronate treatment on biochemical markers of bone remodelling and bone mineral density (BMD) were studied in 30 Caucasian women (postmenopausal for at least 3 years, age 42-76 years, with BMD of the lumbar spine at least 2 S.D. below the mean for mature, premenopausal women). The patients were randomly assigned to receive alendronate (10 mg/day) or placebo for 12 months (double blind). The study was subsequently extended to a second year of open alendronate treatment. The treatment with alendronate resulted in a significant and progressive increase in BMD of the lumbar spine and femoral neck. Under the treatment, the maximal decrease of biochemical markers of bone remodelling (osteocalcin in plasma, bone-specific alkaline phosphatase, N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen in serum, and cross-linked amino-terminal N-telopeptide and total hydroxyproline in urine) was observed at 6 months with no further change during the 2-year period. There were no significant differences in discriminating between patients treated for 1 year with alendronate or placebo using either the percentage change in spine BMD at month 12, or a single measurement of the marker at month 6, or log (percent of baseline at month 6 of value of the marker). In this respect, the power of all the biochemical markers were comparable. The markers are a valuable adjunct to the measurements of BMD, especially in the patients not showing an increase of 3% or more at the lumbar spine BMD after 1 year of treatment.     

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

BACKGROUND: Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. METHODS: Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. RESULTS: Bone ALP decreased significantly from baseline at 3 months (P 相似文献   

Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): Additional results from the monthly oral therapy with ibandronate for osteoporosis intervention (MOTION) study

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported.Objective: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events.Methods: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, nonin-feriority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed.Results: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were ?75.5% with monthly ibandronate and ?81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in ≤30% of patients per group during this 1-year study.Conclusion: The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.     

The effect of different doses of calcitonin on bone mineral density and fracture risk in postmenopausal osteoporosis

A total of 107 patients were included in the study to determine the effects of different doses of intranasal calcitonin on bone mineral density and fracture risk in postmenopausal osteoporosis. Patients were randomly divided into three groups. All three groups were given 1000 mg/day calcium and vitamin D in adequate doses. Two of the groups, the exception being the placebo group, were also given either 50 IU or 100 IU of calcitonin. The data of 81 patients who completed the 24 months of regular study treatment and controls were evaluated. When compared, both of the calcitonin groups were superior to the placebo group regarding increase in bone mineral density and decrease in fracture rate.     

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline N-telopeptide of type l collagen (NTX ) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGF &#103 2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX ) as well as bone resorptive cytokines (IL-11,TGF &#103 2 ). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis. (Pyr), deoxy-pyridinoline (DPyr) and     

Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis.

Treatment effects on bone quality and remodeling was assessed in postmenopausal women with osteoporosis treated with oral alendronate. One transiliac bone biopsy was obtained from 231 women at either 24 mo (n = 11) or 36 mo (n = 120) from the start of treatment with alendronate at doses of between 5 and 20 mg/d, or placebo. 64 biopsies at 24 mo (31 from the placebo group and 33 alendronate-treated patients) and 95 biopsies at 36 mo (40 from the placebo group and 55 alendronate-treated patients) provided adequate cancellous tissue, and were analyzed by histomorphometry. Mineral apposition rate was unaffected by treatment. At 24 and 36 mo, osteoid thickness, volume, and surface significantly decreased. At each of the doses studied, mineralizing surface and activation frequency significantly decreased at each time point (e.g., -92% and -87%, respectively, for the 10 mg daily dose after 2 yr). These diminutions were of the same magnitude for each dose at 24 mo, and for the two highest doses at 36 mo. A significant increase in wall thickness accompanied by a reduction in erosion depth was detected in biopsies obtained at 24 mo. These findings confirm that mineralization is normal, and trabecular bone turnover markedly decreased in patients receiving long-term dosing with alendronate. The findings also suggest that the observed increases in bone mineral density could result both from a reduction in the remodeling space due to a decreased activation frequency and a possible trend to a positive bone balance. In addition, further studies focused on a possible increase in the degree of mineralization of bone are required.     

The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.     

Markers of bone turnover do not predict bone metastases in breast cancer

Markers of bone turnover are often elevated in patients with prevalent bone metastases (BM). To test whether bone markers may be used as early indicators of developing BM, we prospectively studied 113 women with primary breast cancer. At the time of study inclusion, none of the women had BM, skeletal disease or was on bone active drugs. During follow-up (8-52, median 30 mo.), pt. were seen every 3 mo. and blood/urine specimens were obtained. Eleven patients developed BM (BM+) and each of them was matched to 4 women remaining free of BM (BM-). Markers were serum (s) calcium, sTAP, sBAP, sOC, sPICP, sNTX, sCTX and urinary (u) PYD, uDPD, uNTX, uCTX. All analyses were done in single batches after study end. At any given point in time, marker levels in the BM+ group did not differ from those in the BM- group. Levels at baseline did not predict later BM (OR 0.14-1.01, all ns). 93% of all changes in bone markers were below the least significant change, as defined in an independent group of similar patients. The remaining 7% of values could not be associated in a consistent pattern with the occurrence of BM. We conclude that in patients with primary breast cancer, biochemical markers of bone turnover can not be used to predict or diagnose incident BM. This lack in diagnostic validity is mainly attributable to the high overall and long-term variability of the currently used bone markers.     

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis.

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis.     

绝经后2型糖尿病女性雌激素水平与骨质疏松的相关性研究

【目的】探讨绝经后2型糖尿病（T2DM）合并骨质疏松（OP）妇女雌激素水平及骨密度的变化及其相关性。【方法】120例绝经后女性T2DM患者根据骨密度值分为骨密度正常组即T组（62例）,骨质疏松组即P组（58例）。另选取60例血糖及骨密度均正常的绝经后女性作为正常对照组,即N组（60例）。比较三组骨代谢、糖代谢及性激素等指标。【结果】P组骨碱性磷酸酶（sBAP）、骨钙素（sOC）、Ⅰ型胶原交联C 端肽（sCTx）和尿Ⅰ型胶原交联N 端肽（uNTx）明显低于T组。P组与T组、N组比较,血清卵泡刺激素（FSH）、促黄体激素（LH）升高,雌二醇（E2）下降（ P＜0．05）。相关性分析显示,患者O P与糖尿病病程、年龄、糖化血红蛋白（HbA1C）、空腹血糖（FPG）、FSH、LH、uNTx与肌酐（Cr）呈显著负相关,与sBAP、sOC、sCTx无相关性。【结论】绝经后T2DM妇女骨质疏松与糖代谢及雌激素水平有关。     

Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized,double-blind,placebo-controlled study

OBJECTIVE: To compare the upper gastrointestinal (GI) tract tolerability of once-weekly oral alendronate, 70 mg, and placebo. PATIENTS AND METHODS: This was a 12-week multicenter, randomized, double-blind, placebo-controlled study. The first patient initiated treatment on June 5, 2000, and the last patient completed treatment on March 1, 2001. The study enrolled 450 postmenopausal women and men with osteoporosis (224 took alendronate, 226 took placebo) who were ambulatory and community dwelling at 48 outpatient study centers in the United States. By design, approximately half of the patients were naive to bisphosphonates. The primary end point was upper GI tract tolerability based on the incidence of any upper GI tract adverse events. Secondary end points included the number of discontinuations due to drug-related upper GI tract adverse events and the change from baseline in bone resorption, assessed by the urinary N-telopeptide-creatinine ratio at 12 weeks. A subgroup analysis of the primary and secondary end points was performed on the patients stratified by prior bisphosphonate use. The safety and tolerability of the weekly alendronate and placebo regimens were captured as clinical and laboratory adverse events. RESULTS: A total of 11% of the alendronate patients and 13% of the placebo patients reported an upper GI tract adverse event. Discontinuations due to drug-related upper GI tract adverse events occurred in 3% of alendronate patients and 1% of placebo patients. The differences between the treatment groups for the primary and secondary end points were not significant. For the primary end point, the upper limit of the 95% confidence interval of the difference was well within the prespecified 14% comparability bound (-2.2%; 95% confidence interval, -8.3% to 3.9%). The overall incidence of upper GI tract adverse events was lower in the subgroup of patients with prior bisphosphonate exposure (8%) than in those who were bisphosphonate naive (16%). However, regardless of prior bisphosphonate exposure, the incidence of upper GI tract adverse events was similar between the alendronate and placebo patients. The urinary N-telopeptide-creatinine ratio showed a significant decrease in the alendronate patients (72% of baseline, P<.001) compared with a slight increase in the placebo patients (106% of baseline) at week 12. CONCLUSION: In this 3-month study, the incidence of upper GI tract adverse events in patients treated with once-weekly alendronate, 70 mg, was comparable to that with placebo.     

Clinical and biological effects of low doses of (3 amino-1 hydroxypropylidene)-1,1-bisphosphonate (APD) in Paget''s disease of bone

Abstract. At doses varying between 500 and 1500 mg/day, the disodium salt of (3 amino-1 hydroxypro-pylidene)-1,1-bisphosphonate (APD) has been shown to induce rapid and complete biochemical responses in Paget's disease of bone, but a short-lived and self-limited fever has been observed in 30–40% of patients. The present study is an open and unrandomized trial, performed to explore the use of lower doses of APD (250 and 50 mg/day) given for 6 months to fourteen patients suffering from Paget's disease of bone. Subjective clinical improvement and complete biochemical remission (as assessed by normalization of urinary hydroxyproline excretion and plasma alkaline phosphatase concentration) was observed in ten out of eleven patients given 250 mg/day, but fever did not occur. Thus, a significant decrease in urinary hydroxyproline excretion was noted as early as 15 days after the beginning of the treatment (from 4.5 to 1.3 μmol/l GF; P > 0.05) whereas plasma alkaline phosphatase concentration fell significantly only 1 month later (from 330 to 195 IU/ml; P > 0.05). Both mean (± SEM) urinary hydroxyproline excretion (0.98 ± 0.08 μmol/l GF) and plasma alkaline phosphatase concentration (70 ± 8 IU/ml) were in the normal range after 6 months of treatment. Plasma calcium and phosphorus concentration, urinary calcium excretion and TmP/GFR decreased whereas plasma immunoreactive parathyroid hormone concentration increased. These changes were statistically significant (P < 0.05) only transiently and disappeared at the time when bone formation (assessed by plasma alkaline phosphatase) returned to normal. An increase in total body retention of ⁴⁷Ca during the second month of treatment was documented in five patients (P < 0.05), compatible with a positive calcium balance. Plasma immunoreactive calcitonin did not change (P > 0.05). After 6 months of treatment at 50 mg/day, APD also induced significant decreases in urinary hydroxyproline excretion (from 4.23 to 1.73 μmol/l GF; P < 0.05) and plasma alkaline phosphatase concentration (from 360 to 162 IU/ml; P < 0.05) but biochemical remissions were not complete and these two variables were significantly higher than the corresponding values in the group of patients receiving 250 mg APD/day. Less marked changes were also noted in all the other variables measured. Biological and clinical tolerance was good in all the patients. It is concluded that 250 mg/day of APD is an effective dose schedule, capable of reducing to normal levels the indirect indices of bone turn-over, but in contrast with higher doses, without inducing fever.     

阿仑磷酸钠联合复方丹参片治疗绝经后骨质疏松症患者的效果评价

目的 探讨复方丹参片联合福善美(阿仑磷酸钠)治疗妇女绝经后骨质疏松症,评价其疗效及安全性.方法 将180例绝经后骨质疏松症患者随机分为福善美组、丹参组和复方丹参片联合福善美组(简称联合组).分别采用相应药物进行治疗,疗程6个月,比较2组碱性磷酸酶、骨钙素、尿钙、尿肌酐、尿羟脯氨酸含量及腰1～5骨密度值.结果 联合组的碱性磷酸酶、骨钙素、尿钙、尿肌酐、尿羟脯氨酸、腰1～5骨密度值与其他2组比较差异显著.结论 福善美联合复方丹参片治疗绝经后妇女骨质疏松症安全有效.

Abstract：

Objective To assess whether treatment with compound danshen tablets plus alendronate would be safe and effective in women with postmenopausal osteoporosis. Methods 180 women with postmenopausal osteoporosis were randomized to receive combination therapy and independent therapy with compound danshen tablets and alendronate for 6 months. Scores of VRS were assessed,mean serum alkaline phosphatase, serum osteocalcin, urinary creatinine, urinary hydroxyproline, urinary calcium were detected. Bone mineral density of lumbar vertebra 1 ~5 was determined by dual X - ray absorptiometry. Results Mean serum alkaline phosphatase, serum osteocalcin, and urinary creatinine, urinary hydroxyproline, urinary calcium were statistically different between the combination therapy group and the independent therapy group, and bone mineral densities increased in all therapy groups while there was higher elevated level in the combination therapy group. Conclusions The combination therapy of compound danshen tablets with alendronate has a favorable influence on women with postmenopausal osteoporosis.     

A 5-year controlled randomized study of prevention of postmenopausal trabecular bone loss with nasal salmon calcitonin and calcium

Abstract. The aim of this paper was to evaluate the long-term (5 years) efficacy of nasal salmon calcitonin in prevention of trabecular postmenopausal bone loss, which was a follow-up of a previously published study (3 years); a randomized, controlled group comparison. One hundred healthy postmenopausal women were randomly chosen from those (186) having completed the 3 year protocol. The 100 women were allocated to an additional 2 year period (total of 5 years) of treatment with either 500 mg d^-1, 5 days week^-1 of calcium or the same amount of calcium plus 50 IU d^-1, 5 days per week of nasal salmon calcitonin, 87 (87%) women complied with the protocol throughout. The main outcome measures were the bone mineral density of the lumbar spine (1-BMD) (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine and hydroxyproline/creatinine ratios). The women receiving calcium alone presented a significant decrease in 1-BMD after 6 months [– 1·6 (0·5)%] [mean(SEM)] (P < 0·01) and this decrease remained significant after 36 months [– 6·1(0·8)%] (P < 0·01) and until the end of the trial [– 6·6(1·0)% at t60] (P < 0·01). In women receiving calcium and calcitonin, 1-BMD significantly increased after 36 months [+ 2(0·7%] (P < 0·01) and 42 months [+ 2·5(0·7)%] (P < 0·01) and was unchanged at the other times of investigation [+ 1·1(1·1)% at t60] (NS). The evolution of BMD in the two groups was highly significantly different (P < 0·001) since the sixth month of the study and remained so until the end of the study. No differences were observed in the biochemical parameters reflecting bone turnover. Nasal administration of salmon calcitonin, using a low-dose (50 IU d^-1), intermittent (5 days week^-1) regimen, may totally prevent postmenopausal bone loss, at the level of the lumbar spine, for at least 5 years, if the treatment is continued for this duration. It is not clear whether the results observed during the fourth and fifth years are fully attributable to calcitonin or if calcium by itself plays also a protective role against trabecular bone loss.     

Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females

Abstract. With the aim of preventing postmenopausal bone loss, a placebo-controlled double-blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17β-oestra-diol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D₃); fluoride and D₃; and lα (OH) vitamin D3 0–25 μg/day (lαD₃). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%).
The combined placebo groups snowed a linear fall in BMC reaching 3-3 % after 2 years ( P < 0–001). Hormones and hormones and thiazide led to a 2–5% gain in BMC ( P < 001). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1–5% ( P < 0–05), less than that of the placebo group ( P < 0–05). BMC declined by 3–6%, 4–5%, 3–7% and 3–7% during the respective use of fluoride, D₃, fluoride and D₃ and lαD₃. Nevertheless, the urinary calcium excretion during lαD₃ and D₃ treatment was 1-1-5 mmol/day higher than in the placebo groups.
Apparently, there is no real alternative to oestro-gen/gestagen in the prevention of postmenopausal osteoporosis.     

Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females

Abstract With the aim of preventing postmenopausal bone loss, a placebo-controlled double-blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17β-oestra-diol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D₃); fluoride and D₃; and lα (OH) vitamin D3 0–25 μg/day (lαD₃). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%).
The combined placebo groups snowed a linear fall in BMC reaching 3–3 % after 2 years ( P < 0–001). Hormones and hormones and thiazide led to a 2–5% gain in BMC ( P < 001). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1–5% ( P < 0–05), less than that of the placebo group ( P < 0–05). BMC declined by 3–6%, 4–5%, 3–7% and 3–7% during the respective use of fluoride, D₃, fluoride and D₃ and lαD₃. Nevertheless, the urinary calcium excretion during lαD₃ and D₃ treatment was 1–1–5 mmol/day higher than in the placebo groups.
Apparently, there is no real alternative to oestro-gen/gestagen in the prevention of postmenopausal osteoporosis.     

利维爱对绝经后妇女骨密度及骨代谢指标的影响

目的了解利维爱对绝经后妇女骨密度及骨代谢指标的影响 . 方法将 123例自然绝经后妇女随机分 2组 研究组每日口服利维爱 1.25 mg+ 钙尔奇 D 600 mg, 对照组每日口服钙尔奇 D 600 mg, 观察 12个月 . 用药前后分别检测腰椎 (L 2～ 4)及股骨颈 (NK)骨密度 (BMD)骨代谢指标血清骨钙素 (BGP)和碱性磷酸酶 (AKP)及尿吡啶酚 /肌酐 (Pyr/cr)和钙 /肌酐 (Ca/Cr)比值 . 结果 (1)L 2～ 4、 NK两部位 BMD 研究组治疗后均增加 , 且前者上升有显著性差异 (P< 0.05);对照组均下降无显著性差异 (P >0.05);治疗后 2组间比较有显著性差异 (P< 0.01,P< 0.05). (2)生化指标血 BGP、 AKP及尿 Pyr/Cr、 Ca/Cr 治疗后研究组均上升有显著性差异 (P< 0.01,P< 0.05); 对照组变化无显著性差异 (P >0.05). 结论绝经后妇女每日服用 1.25 mg利维爱加钙尔奇 D可以提高骨量 ; 单用钙尔奇 D不能防止骨丢失 .     

渐进抗阻训练结合阿仑膦酸钠提高绝经后骨质疏松症患者腰椎骨密度的初步研究

目的观察渐进抗阻训练结合阿仑膦酸钠疗法对提高绝经后骨质疏松症患者腰椎骨密度的效果。方法20例绝经后骨质疏松症患者随机分为A、B两组,各10例,A组接受渐进抗阻训练结合阿仑膦酸钠治疗,B组仅接受阿仑膦酸钠治疗,疗程均为3个月。治疗前后用双能X线吸收仪分别测量腰椎骨密度。结果治疗前,两组患者的骨密度差异无显著性意义;治疗3个月后,A组患者的腰椎骨密度提高(4.520±0.68)%,B组提高(0.100±0.01)%,两组间的差异有非常显著性意义(P<0.01)。结论渐进抗阻训练结合阿仑膦酸钠疗法可提高绝经后骨质疏松症患者腰椎的骨密度,效果明显优于单纯服用阿仑膦酸钠。     

Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis

We have studied the clinical usefulness of urinary bone resorption markers in postmenopausal women with symptomatic osteoporosis. The study design is a randomised double-blind placebo controlled study, in which the subjects were daily treated for 24 months either with a hormone analogue (2.5 mg Livial, generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14, age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n = 19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD) and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the urine assay results were calculated per mmol creatinine. All the resorption markers decreased during the two-year study period in both groups. The Z scores (discriminating power, i.e. ability of the different tests to distinguish the hormone treated subjects from the placebo treated subjects) for HOP and PYD were rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the two treatment groups were statistically significant for DPD at 12 and 24 months of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45-1.90. NTx showed the most prominent decrease from the beginning of the study especially in the hormone treatment group: the differences between the two treatment groups were statistically highly significant for NTx already at 6 months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11-3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the lumbar spine and femoral neck did not show statistically significant differences between the two treatment groups throughout the two-year study period. After 2 years there was, however, a significant increase in bone density both in the spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the women with hormone treatment. In the control group a significant increase (+ 5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.) in the femoral neck was observed. We suggest that measurement of urinary cross-linked peptides derived from Type I collagen (NTx and DPD) might be a useful biochemical method of observing the positive clinical effect (i.e. reduction in bone resorption) following hormone replacement therapy in postmenopausal fracture patients.     

Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial

OBJECTIVES: To determine the efficacy of alendronate treatment on risk of vertebral fracture in a subgroup of women from the Fracture Intervention Trial who had bone mineral density T scores between -1.6 and -2.5 at the femoral neck and to describe how soon after initiation of therapy alendronate becomes effective and whether it is consistent in women with and without existing radiographic vertebral fracture. PATIENTS AND METHODS: From May 1992 to March 1997, postmenopausal women aged 55 to 80 years were randomized to receive alendronate at 5 mg/d for 2 years and 10 mg/d thereafter or placebo for up to 4.5 years (mean, 3.8 years) in a controlled, double-blind, multicenter study. RESULTS: A total of 3737 postmenopausal women were included in the study, 1878 in the alendronate group and 1859 in the placebo group. Risk of vertebral fracture was significantly reduced by alendronate compared with placebo for clinical (relative risk [RR], 0.40; 95% confidence interval [CI], 0.19-0.76; P=.005) and radiographic (RR, 0.57; 95% CI, 0.41-0.81; P=-.002) fracture. The reductions in vertebral fracture risk were consistent in women with and without an existing radiographic vertebral fracture for clinical (RR, 0.34; 95% CI, 0.12-0.84; and RR, 0.46; 95% CI, 0.16-1.17; respectively) and radiographic (RR, 0.53; 95% CI, 0.34-0.82; and RR, 0.64; 95% CI, 0.38-1.10; respectively) fractures. In both groups, the effect of alendronate on clinical vertebral fracture was noted soon after therapy was initiated. The absolute risk of vertebral fracture was low in women without a baseline radiographic fracture. CONCLUSIONS: In women with low bone mass who do not meet the bone mineral density criterion for osteoporosis, alendronate is effective in reducing the risk of vertebral fractures. The absolute benefit of this therapy in women with a T score between -1.6 and -2.5 is greater in women with an existing vertebral fracture and/or with other risk factors. The effect of alendronate occurs early.