骨吸收抑制剂治疗绝经后骨质疏松的临床评价

目的　评价不同类型骨吸收抑制剂在临床原发性骨质疏松症治疗中的疗效。方法　30 0例原发性骨质疏松症患者分成三组 ,每组 10 0例 ,所有患者均排除继发性骨质疏松。性激素类组 :服用利维爱 2 5mg ,隔日 1次 ;降钙素组 :密钙息 5 0IU ,肌注 ,第 1周每天 1次 ,第 2周隔日 1次 ,以后每周 2次 ;二膦酸盐组 :阿仑膦酸钠 10mg ,每天 1次。治疗 2年后随访 :腰椎骨密度 (BMD)、胫骨骨超声 (QUS)、尿羟脯氨酸 (HOP)、骨钙素和新骨折。结果　临床骨痛降钙素缓解速度最快 ,性激素类药物可迅速有效地缓解妇女更年期症状。治疗 2年后 ,腰椎骨密度明显上升 (P <0 0 5 ) ,二膦酸盐组上升 5 1% ,性激素类组上升 4 2 % ,降钙素上升 0 97% ;胫骨骨超声显著提高 (P <0 0 5 ) ,性激素组上升 2 1% ,降钙素组 1 8% ,二膦酸盐组 1 7% ;新骨折共 4例 :二膦酸盐组 2例 ,降钙素组和性激素组各 1例 ;尿羟脯氨酸仅二膦酸盐组明显下降 ;骨钙素各组无明显变化。结论　骨吸收抑制剂是骨质疏松治疗的重要手段 ,性激素类药物是治疗伴有绝经后综合症骨质疏松患者的首选药物 ,二膦酸盐对骨量较低且伴有骨痛的患者有良好的疗效 ,降钙素治疗骨质疏松疼痛临床疗效显著。     

Bone loss following tendon laceration, repair and passive mobilization.

Little is known about the localized changes in bone mass that occur following tendon or ligament injury. Interruption of normal load transfer at the insertion site will presumably lead to a localized loss of bone, although few data exist to support this claim. To test this hypothesis, we transected the canine flexor digitorum profundus (FDP) tendon from its insertion, and either repaired it using a trans-osseous suture technique or left it unrepaired (laceration only). Post-operatively, forelimbs in the repair group were cast immobilized except for 10 min of daily passive mobilization rehabilitation, whereas in the laceration only group dogs were allowed full weight bearing. At 5-42 days post-injury, we assessed bone mineral density (BMD) using pQCT and osteoclast surface by histomorphometry. We measured significant bone loss in the distal phalanx after combined FDP tendon laceration, repair, and post-operative passive mobilization, with BMD decreases of 20%, 40%, and 41% at 10, 21, and 42 days (p<0.01). Moreover, we observed that passive mobilization and tendon laceration each contributed independently to the observed bone loss. At 42 days, BMD was reduced by 21% in bones that were not injured but were subjected to the post-operative passive mobilization protocol, while BMD was reduced by 28% in bones subjected to tendon laceration and full weight bearing (p<0.01). In both the passive mobilization and laceration specimens, we counted significantly increased osteoclasts after only 7-10 days, and these increases persisted through 42 days (p<0.05). We conclude that rapid and sustained bone resorption leads to significant bone loss in the 6-week period following flexor tendon injury and repair. This bone loss may impact healing by impeding the restoration of a strong tendon-bone interface.     

Efficacy of low-dose,intermittent eel calcitonin treatment for osteoporosis

The efficacy of low-dose intermittent calcitonin treatment for osteoporosis was evaluated. Twenty subjects (19 women, 1 man, mean age 59.1 ± 8.1) who exhibited osteopenia on plain X-ray were treated once a week with either a 10-IU or 20-IU i.m. injection of eel calcitonin (Elcatonin). Bone mineral density (BMD) of the lumbar spine as determined by dual photon absorptiometry significantly increased in the 20-IU group at 3 (7.2%) and 6 (10.7%) months, while the results were not significant in the 10-IU group (2.0% and 2.4%, respectively). Forearm BMD assessed by single photon absorptiometry did not change significantly in either group. The urinary hydroxyproline/creatinine ratio was significantly suppressed in both groups (P < 0.05). Serum bone Gla-protein showed a tendency to increase at 6 months in both groups. Spontaneous back pain disappeared by the end of this study in all patients who received 20IU per week, although it persisted in some of the patients in the 10-IU group. These results suggest that low-dose, intermittent calcitonin is effective at least after 6 months in the treatment of osteoporosis with a minimum dose of calcitonin at 20IU per week.     

Transmission Disequilibrium Test for Hand Bone Mineral Density and 11q12-13 Chromosomal Segment

The main aim of the present study was to test the hypothesis that the bone mineral density (BMD) assessed from radiographs of the hand phalanges in a random sample of ethnically homogeneous pedigrees is linked to the 11q12-13 chromosomal segment. The data for the study were gathered from 574 Chuvasha individuals belonging to two- and three-generation pedigrees who live in small villages in the Bashkortostan autonomy, Russia. Preliminary statistical-genetic analysis of the BMD in the pedigrees studied showed that potential genetic effects were highly significant (p<0.001, in comparison with the model assuming no genetic effect), and explained at least 36% of the BMD variation adjusted for sex and age differences. For the transmission/disequilibrium test (TDT) used in our study, a total of 163 nuclear families with two sibs on average were available. Seven DNA microsatellite markers (D11S1313, D11S1765, D11S987, D11S913, D11S983, D11S1314, D11S916) with average spacing of 2 cM on the chromosomal area 11q12-13 were selected for the TDT. The nominal p values (p<0.05–0.0015) obtained from three TDT-type tests used for random and extreme-threshold sampling designs pointed consistently to possible linkage disequilibrium between BMD and some of the DNA markers. There was evidence for possible linkage disequilibrium in the upper part of the chromosomal segment studied (markers D11S1313 and D11S1765), and also in the lower part (markers D11S1983 and D11S1314). The lowest nominal p values (0.0015–0.0067) were obtained from three TDT-type tests for marker D11S1313. However, our findings must still be treated with great caution. Received: 19 September 2001 / Accepted: 6 December 2001     

广州地区中老年人群骨量减少及骨质疏松患病率的调查

目的：了解广州地区中老年人骨量减少（Osteopenia）及骨质疏松（Osteoporosis,OP），患病率的变化规律，为防治OP提供科学依据。方法：居住广州市内及郊区农村20年以上的40岁以上人群进行整群随机抽样，样本共1160人，准确记录其性别和年龄后，用美国Lunar公司的DEXA测试受试者L2－4和髋部的骨密度（BMD），然后进行统计、比较与分析。结果：40岁组女性L2－4及Ward‘s区BMD高于男性，该组骨量减少患病率男女性都超过样本数的1／3，50岁以男性高于女性，男性70岁组L2－4下降才明显，女性L2－4及髋部BMD从50岁起加速下降，L2－4BMD70岁以后减慢，男性60岁以后髋部BMD下降明显，不论男、女性髋部BMD下降直到80岁以上都较显著，骨质疏松患病率随年龄的增长而增加，女性50岁组起变化开始明显，60岁组OP患病率85％，并一起以重度OP占多数，农村患病率高于城市，男性在70岁组起OP患病率显著上升，结论：广州地区中老年人骨量减少及OP患病率与北京、上海、成都等地区近似，老年女性以重度OP占多数，50岁以上男性OP患病率达到30％，应得到足够的重视。     

Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study

The efficacy and safety of treatment with oral alendronate (ALN) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind, randomized, multicenter study of Japanese patients with involutional osteoporosis. The primary efficacy end point was the percent change from baseline in the lumbar spine (L1–L4) bone mineral density (BMD) after 52 weeks of treatment. In this study, 328 patients were randomized to ALN 5 mg once daily (160 patients) or ALN 35 mg once weekly (168 patients). The adjusted mean percent change from baseline in lumbar spine (L1–L4) BMD after 52 weeks of treatment was 5.8% and 6.4% in the once-daily group and the once-weekly group, respectively (both P < 0.001). The 95% confidence interval for the difference in spine BMD change between the two treatment groups was −0.31% to 1.48%, indicating that the two regimens were therapeutically equivalent, since the confidence interval fell entirely within the predefined equivalence criterion (±1.5%). The time course of the spine BMD increase was also similar for both regimens. Regarding total hip BMD, mean changes from baseline at 52 weeks were 2.8% and 3.0% in the once-daily group and the once-weekly group, respectively. In addition, the bone markers (urinary deoxypyridinoline, urinary type-I collagen N-telopeptides, and serum bone-specific alkaline phosphatase) were reduced to a similar level by either treatment throughout the treatment period. The tolerability and safety profiles were also similar between the treatment groups. Taken together, we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen.     

Association of estrogen receptor α gene microsatellite polymorphism with annual changes in bone mineral density in Korean women with hormone replacement therapy

Variation in drug response to hormone replacement therapy (HRT) may reflect genetic heterogeneity in the estrogen-related genes, possibly including estrogen receptor alpha (ERα) gene. However, only a few association studies of the drug response to HRT have been reported, focusing mainly on the intronic polymorphisms of the ERα gene. We therefore examined 284 postmenopausal women (mean age, 52.2 ± 5.0 years) for the microsatellite thymine–adenine (TA) repeat polymorphism in the promoter of the ERα gene and its relationship to drug response by measuring changes in bone mineral density (BMD) after 1 year of HRT. In our study population, the most common number of TA repeats was 14, with a range of values between 11 and 27. At baseline, the number of TA repeats was neither associated with measured lumbar spine or femoral neck BMD nor with bone markers. When we categorized the subjects by the TA repeat numbers into an L group (n = 142), with a low mean number of repeats (TA < 16), and an H group (n = 142), with a high mean number of repeats (TA ≥ 16), no significant genotypic differences were noted in spinal or femoral neck BMD or in bone markers. However, the drug response on lumbar spine BMD after 1 year of HRT correlated with the mean number of TA repeats (r = −0.131, P = 0.035) after adjustment for confounding factors such as body mass index and years since menopause. This correlation was also seen with the number of TA repeats on the shorter allele (r = −0.159, P = 0.012), which was defined as the allele with the lower number of TA repeats. However, this genotypic association was not found in the femoral neck BMD (r = 0.053, P = 0.396). When we defined the nonresponder group as women who had lost BMD even with HRT, 15.9% of the subjects were included, and this group was significantly younger and had higher initial BMD than the responder group. After further adjustment for age and initial BMD, the number of TA repeats on the shorter allele remained significantly associated with drug responsiveness (P = 0.005). These data indicate significant effects of the ERα TA repeat polymorphism on the estrogen responsiveness of lumbar spine BMD after 1 year of HRT in Korean women.     

Establishment of BMD reference curves at different skeletal sites in women, using a Cartesian coordinate numeration system

The BMD reference curve is the reference value used for diagnosing osteoporosis and assessing bone mass changes. Its accuracy would affect the correctness of T -score and Z -score values and thus the reliability of diagnostic results. In this paper, we report the use of a new method, a Cartesian coordinate numeration system, to establish BMD reference curves at different skeletal sites in women. In a reference population of 3,919 women ranging in age from 5–85 years, we used the dual X-ray absorptiometry (DXA) bone densitometer to measure BMD at the posteroanterior spine (PA; vertebrae L1–L4), followed by a paired PA/lateral spine scan of the vertebral bodies of L2–L4, expressed in g/cm² and g/cm³, and of the hip and forearm. We chose the cubic regression model to best fit BMD curves that varied with age at different skeletal sites. We then referred the BMD of the fitting curves established by the method of the coordinate numeration system as reference curves, compared them to BMD reference curves derived from the fitting curve equation or age cross-section, and calculated the deflection degrees of the BMD reference curves acquired from the fitting curve equation. At the PA spine, lateral spine (expressed in g/cm³), femoral neck, Wards triangle and radius + ulna ultradistal, the reference curves calculated from the equation were significantly lower than those confirmed by the method of the coordinate numeration system; whereas, at the lateral spine (expressed in g/cm²), total hip, and radius + ulna 1/3 sites, the reference curves derived from the equation were markedly higher than those acquired from the coordinate numeration system. The differences in the two kinds of reference curves calculated by these two different methods gradually increased along with the increment in ages of the women. At the peak value of the reference curves, the BMD calculated from the equation deflected from 2.02% to –10.0% from the BMD acquired from the coordinate numeration system at different skeletal sites, and from 21.5% to –121.8% until the age of 85 years. The highest positive deflection of 65.2% existed at the lateral spine (expressed in g/cm²) and the lowest positive deflection of 21.5% at the total hip. The maximum negative deflection of –121.8% was at the radius + ulna ultradistal, and the minimum negative deflection of –32.6% at the PA spine. The BMD curve acquired from age cross-section was highly positive compared with the one derived from the coordinate numeration system ( r =0.955–0.985 p =0.000) with no significant difference between them. Various analysts used such a method to obtain the coefficient of variance (CV) in BMD precision on each curve that was from 0.05–0.19%. Our study shows that the Cartesian coordinate numeration system is an accurate, precise and reliable method and can serve to reveal the serious drawbacks of using the fitting curve equation to calculate BMD. The BMD reference curves established by this coordinate numeration system maintained the authenticity of the fitting curve, whereas, using the fitting curve equation to obtain BMD reference curves at different skeletal sites led to distortion, and resulted in false increases or decreases in T -score and Z -score values.     

Correlation between forearm bone mineral density and body composition in Japanese females aged 18–40 years

Objective The purpose of this study was to clarify the relationship between forearm bone mineral density (BMD), body mass index (BMI), and body composition focusing on body fat percentage (BF%) in Japanese females 18 to 40 years old. Methods Subjects were 2,280 females 18–40 years old. Anthropometric measurements were taken, and a medical history was obtained by questionnaire, including age at the time of the study and age at menarche. BF% was measured by bioelectrical impedance analysis. Forearm BMD was measured using dual-energy X-ray absorptiometry (DXA). The correlations of BMD with BMI and BF% were analyzed using a structural equation model. Results The standardized regression coefficients for the path from BMI to BMD and the path from BF% to BMD were 0.538 and −0.184 respectively. The squared multiple correlation of BMD was 0.146. In addition, the standardized regression coefficient for the path from BMI to BF% was 0.896. Conclusion The results showed a positive correlation between BMD and BMI and an inverse correlation between BMD and BF%. At the same time, it was noted that BF% increased with BMI. This indicated that BMD is dependant on BF% in subjects who have a similar BMI. Therefore, this study concluded that it is necessary to take body composition measurements into account when examining the relationship between BMI and BMD, especially in young females.     

Bone mineral density and total body bone mineral content in 18- to 22-year-old women

One hundred sixty-four (164) healthy, young Caucasian women enrolled as midshipmen at the United States Naval Academy with no known disease or bone injury were followed for 3.6 years. Change in bone mineral density (BMD) of the hip, lumbar spine and distal tibia, and total body bone mineral content (TBMC) was measured by dual energy X-ray absorptiometry (DXA). Bone mineral density and TBMC of these women were measured within 2 months (60 ± 4 days) of entering the Academy and annually. Over the study period, hip BMD increased 2.26% (P < 0.001), lumbar spine BMD increased 3.27% (P < 0.001) and distal tibia BMD increased 5.2% (P < 0.001). Total body bone mineral content showed a 5.25% (P < 0.001) increase during the study period. In this group of young women, gain in BMD and TBMC continued until age 22. These results suggest that bone mass may accrue in certain groups of women beyond age 22. The significance of this increase in bone mass during early adulthood on risk for osteoporotic fractures in later life and its impact on exercise-related bone injuries are unknown and warrant further examination.