Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.     

Relationship of bone turnover parameters,endogenous hormones and vit D deficiency to hip fracture in elderly postmenopausal women

Hip fracture is one of the severest consequences of osteoporosis affecting elderly women, but abnormalities of bone turnover responsible for bone loss have not been clearly defined. This study evaluated the relationship of bone turnover parameters to hip fracture in postmenopausal elderly women. We also investigated the effects of endogenous hormones and vitamin D deficiency on osteoporotic hip fracture. The subjects were 21 osteoporotic patients with hip fracture (study group) and 20 healthy postmenopausal women (control group). We measured osteocalcin levels, total and bone alkaline phosphatase (T-ALP and B-ALP), calcitonin, intact parathyroid hormone (iPTH), serum 25 hydroxyvitamin D (25OHD), urinary free deoxypyridinoline (D-pyr) and cross-linked N-telopeptides of type 1 collagen (NTx) levels. Serum T-ALP and B-ALP levels in the study group were lower than those of the control group. The mean serum 25OHD levels in the study group were not significantly different from the control group, but in five cases the mean serum iPTH level was increased. The mean urinary NTx levels were significantly increased in the study group compared with the control group (p<0.05). There was no significant increase in urinary free D-pyr between the two groups. There was significant correlation between serum T-ALP levels and B-ALP levels and between serum iPTH levels and B-ALP levels. The mean serum SHBG level in the study group was higher than in the control group (p<0.05). These data suggest that postmenopausal hip fracture patients have biochemical evidence of decreased bone formation and increased bone resorption compared with postmenopausal healthy subjects. We suggest these abnormalities play a role in the decrease of bone mass and the consequent increase in bone fragility that characterises osteoporotic hip fracture.     

Quantitative bone ultrasound at phalanges and calcaneus in osteoporotic postmenopausal women: influence of age and measurement site

Phalangeal and calcaneal quantitative ultrasound (QUS) measurements were tested in a postmenopausal osteoporotic population of a wide age range to assess their ability to identify subjects with vertebral fractures in a population of postmenopausal women with osteoporosis. A group of 127 osteoporotic women aged from 50 to 85 y, who had been postmenopausal for at least 5 y, were enrolled. All subjects underwent phalangeal and calcaneal QUS measurements, femoral neck and lumbar spine dual energy X-ray absorptiometry (DXA) measurements and lateral thoracic and lumbar spine radiography. Osteoporosis was defined on the basis of femoral neck or lumbar spine bone mineral density (BMD) T-score lower than -2.5 SD or of the presence of one or more vertebral atraumatic fractures, independently of BMD values. Fifty-two women had one or more vertebral fractures, while the remaining 75 had no evidence of previous fracture. Both QUS techniques were able to discriminate between fractured and nonfractured subjects in the whole group (p < 0.05). When patients aged <70 y (n = 43) and patients aged > or = 70 y (n = 84) were considered separately, phalangeal QUS and lumbar spine BMD were able to discriminate vertebral fractures in the younger group (p < 0.05), whereas calcaneal QUS was able to discriminate vertebral fractures in the older one (p < 0.05). The results of this study raise an issue of the optimal use of different QUS techniques and different skeletal sites in the management of osteoporosis in early or late postmenopausal life.     

Performance of Five Phalangeal QUS Parameters in the Evaluation of Gonadal-Status,Age and Vertebral Fracture Risk Compared with DXA

The aim of this cross-sectional study was to study the value of five different quantified ultrasound (QUS) parameters—amplitude-dependent speed of sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), fast-wave amplitude (FWA), bone transmission time (BTT) and signal dynamic (SDY)—measured at the phalanges of the hand in discriminating women with vertebral fracture and their relationship with some determinants of bone mass, in particular age and gonadal status compared with lumbar spine and hip dual-energy x-ray absorptiometry (DXA). We included 791 women aged 35–84 y, divided into premenopause, early menopause and late postmenopause groups on the basis of gonadal status and years since menopause (YSM). The presence of vertebral fracture was evaluated radiographically. All QUS parameters were very sensitive to changes in early postmenopause, with a doubled decrease in early postmenopausal with respect to late postmenopause. In particular AD-SoS and BTT decreases were markedly high in the early postmenopause group. In the late menopause group, similar decreases were observed for AD-SoS, UBPI and hip bone mineral density (BMD). In the multiple logistic model, DXA and QUS significantly discriminate women with and without fractures (p < 0.0001); odds ratio (OR) was higher at lumbar spine BMD (OR 4.01), FWA (OR 3.88), AD-SoS (OR 3.81) and total hip BMD (OR 3.77). Even adjusting the logistic model for age, height, weight, lumbar spine and total hip BMD, all QUS parameters remained significantly predictive of vertebral fracture. AD-SoS showed the best performances both in terms of OR and ROC analysis. QUS parameters show a different behavior in evaluating the effect on bone mass of the time since menopause; AD-SoS and BTT showed a high sensitivity to first changes in bone tissue after menopause. After correction for potential confounders, AD-SoS showed the same ability of lumbar spine BMD in discriminating women with or without vertebral fractures and in the prediction of fracture risk. (E-mail: carlina.albanese@uniroma1.it)     

Discriminative ability of total body bone-mineral measured by dual photon absorptiometry

We investigated the discriminative ability of total body bone-mineral expressed as the total body bone-density (TBBD) measured by dual photon absorptiometry (DPA) in 79 healthy premenopausal women, 27 healthy postmenopausal women, and 120 female osteoporotic fracture patients presenting with either Colles' fracture, vertebral fracture or femoral neck-fracture. TBBD was compared to the bone-mineral density of the lumbar spine (BMDspine) also measured by DPA, and to the bone-mineral content of the forearms (BMCforearm) measured by single photon absorptiometry (SPA). TBBD, BMDspine and BMCforearm showed that all the fracture patient groups had significantly reduced bone-mass. Using receiver operating characteristic (ROC) analysis, we found that TBBD had a tendency towards better discriminative ability than BMDspine or BMCforearm with regard to the discrimination between healthy premenopausal women and the three types of osteoporotic fractures (not significant in spinal fracture patients). BMCforearm had an intermediate position, whereas BMDspine had the smallest discriminative ability. TBBD also discriminated better between healthy postmenopausal women and hip-fracture patients than BMDspine or BMCforearm, whereas there was no significant difference between the three methods regarding the discrimination between the healthy postmenopausal women and the Colles' and spinal fracture patients. We conclude that the TBBD measurement by DPA has a discriminative potential which is better than the local spine or forearm measurements.     

Preventing osteoporotic fractures in older people

While fractures at the spine, wrist and hip are regarded as classical osteoporotic fractures, all fragility fractures in the elderly should be considered as osteoporotic once pathological fracture (e.g. metastatic disease) has been excluded. The assessment of fracture risk should take account of specific risk factors in addition to bone mineral density (BMD). The WHO has produced FRAX, a well validated tool that estimates the probability of a major osteoporotic fracture in the next 10 years. The algorithm is specifically designed for primary care. After age and prior fragility fracture, BMD is the next major determinant of fracture risk. Rather than scanning all individuals with a risk factor, measurements should be targeted to those whose probability of fracture lies close to the intervention threshold where knowledge of BMD will influence management. Individuals with a low trauma vertebral fracture or low BMD for age should be investigated for underlying causes of osteoporosis. Secondary causes account for up to 40% of cases of osteoporosis in women and 60% in men. The goal of osteoporosis management is to reduce the future risk of fracture. Lifestyle modification includes measures to reduce falls risk and bone loss such as exercise, adequate dietary calcium and avoidance of smoking and excessive alcohol consumption. All patients with an osteoporotic fracture and those at high risk should be assessed for falls risk. Combined therapy, with calcium and vitamin D, has been shown to reduce hip fracture risk in the frail elderly and should be considered in all older patients who are housebound or in residential care. Alendronate and risedronate are available as once-weekly preparations with evidence for significant reductions in vertebral and non-vertebral fractures. Denosumab is approved for osteoporosis in postmenopausal women at increased risk of fractures. Strontium ranelate has been shown to reduce fracture risk significantly in postmenopausal women.     

Regional bone mineral in healthy and osteoporotic women: a cross-sectional study

Regional bone mineral content and density (BMC and BMD) was measured in six regions (head, arms, chest, spine, pelvis, and legs) using dual photon 153Gd absorptiometry (DPA) in 128 healthy women aged 21-77 years, and in 45 women presenting with Colles' fracture (mean age 65 years), 46 women with vertebral crush or wedge fracture (mean age 68 years), and 27 women with femoral neck-fracture (mean age 74 years). The age-related normal bone loss was generalized, uniformly distributed, and best described by a combination of a premenopausal linear and a postmenopausal exponential regression in all six regions. Looking at BMD, the overall expected bone loss from age 20 to age 80 was approximately 20% in all the regions. When the fracture patients were examined, we found also generalized bone deficit as the prominent feature, amounting to about 20% of the premenopausal level for Colles' and spinal fractures, and about 25% for femoral neck-fracture. However, there was a regional bias in the fracture patients, as the Colles' and spinal fracture patients had a preferential reduction in spinal and pelvic BMD, whereas the patients with femoral neck-fracture had a preferential reduction in pelvic and leg BMD. We conclude that age-related and osteoporotic bone loss is generalized. Furthermore, we propose that regional differences in osteoporotic bone loss are brought about by a simple biological variability of the range of (i) relative amount of trabecular and cortical bone, (ii) rate of loss in the two types of bone tissue, and (iii) time of onset of trabecular relative to cortical bone loss.     

Biochemical markers of bone turnover and response of bone mineral density to intervention in early postmenopausal women: an experience in a clinical laboratory

BACKGROUND: Markers of bone formation and resorption may be useful as early indicators of response to therapy. Our aim in this study was to investigate the use of bone markers for monitoring of intervention for bone loss in early postmenopausal women and to assess the relationships between these markers and changes in bone mineral density (BMD). METHODS: Subjects were randomly assigned to the following groups: a control group; a group receiving calcium alone; groups receiving calcium plus low or conventional doses of conjugated equine estrogen; and groups receiving calcium plus low or conventional doses of calcitriol. At baseline and at 1 and 3 months after intervention, we measured serum intact osteocalcin, serum N-terminal midfragment osteocalcin, serum C-terminal telopeptide of type I collagen (CTx), urinary deoxypyridinoline cross-links, and urinary CTX: The BMD of the lumbar spine and the femoral neck was measured at baseline and after 1 and 2 years of intervention. RESULTS: No marker changed significantly in the control group except urinary CTx, which increased at 3 months. Serum CTx decreased in all regimens at 1 or 3 months of intervention. In addition, the changes of all markers at 3 months were inversely associated with the change in the BMD of the lumbar spine at 1 or 2 years (r = -0.144 to -0.314), whereas only the changes of bone resorption markers at 3 months were inversely correlated with the changes in femoral BMD at 1 or 2 years (r = -0.143 to -0.366). CONCLUSIONS: Biochemical markers of bone turnover appear to be of use in assessing early response to therapy. Bone resorption markers, especially serum CTx, are better indicators than bone formation markers for estimating the response to intervention in early postmenopausal women. However, the early changes in bone markers were weakly related to the later changes in BMD.     

Age-related changes in bone turnover markers and ovarian hormones in premenopausal and postmenopausal Indian women

This study characterizes age-related changes in bone turnover markers in relation to ovarian hormones. The data (N = 236) were divided into 5-year age bands and three groups: premenopausal (Group I, N = 139), perimenopausal (Group II, N = 30), and postmenopausal (Group III, N = 67). Age-related increases in mean parathyroid hormone (PTH), osteocalcin (OC), and collagen telopeptide (CTx) levels were observed. Women in Group II (N = 37) with osteopenia had lower levels of E1G (P<0.001) with normal FSH levels as compared to 50 women in the same group with normal bone mineral density (BMD). Their mean OC levels were reduced (P<0.05) and CTx levels were significantly elevated (P<0.01). The mean E1G levels were significantly lower (P<0.001) and mean CTx levels were significantly higher (P<0.001) in 30 perimenopausal women (Group II) compared to premenopausal women. In 28 postmenopausal women (group III) the mean BMD levels and E1G were significantly lower (P<0.001) with elevated FSH levels (P<0.001). Increased CTx levels (P<0.0001) reflected a higher rate of bone resorption. These observations suggest that perimenopausal women with low E1G, elevated FSH should be screened for osteoporosis, and it may be valid to combine simultaneous measurements of bone turnover markers with ovarian hormones when screening women at risk for osteoporosis.     

Integrating real‐world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real‐world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN‐BMD) were well‐described by a bi‐exponential relationship with first‐order BMD formation (k₁) and resorption (k₂) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25–maximum 53]) lose 0.6% FN‐BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10‐year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN‐BMD of 0.975 g/cm² at menopause, associated with a 10‐year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long‐term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Changes in bone mineral density (BMD) in women due to estrogen decline during menopause and its relationship to the increased risk of bone fractures are well‐established.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What is the magnitude of longitudinal natural change in BMD in untreated premenopausal women and its relationship to the 10‐year fracture risk?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study quantified the magnitude of longitudinal natural decline in femoral neck BMD in premenopausal women across healthy and patient populations and its translation to long‐term postmenopausal fracture risk, using real‐world data (RWD) and clinical trials data coupled with modeling and simulation.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study provides a model‐informed drug development (MIDD) approach that integrates RWD and clinical trials data to evaluate bone health quantitatively and longitudinally in premenopausal women. Our MIDD approach enables prediction of the magnitude of change in BMD and fracture risk due to medical treatments over time to inform the risk‐benefit evaluation of new therapies.     

Activity or mass concentration of bone-specific alkaline phosphatase as a marker of bone formation.

BACKGROUND: Recently published data identified bone-specific alkaline phosphatase (BALP) as a good marker of bone formation in different bone diseases and osteoporosis. Two methods are available for BALP determination: one measures enzyme activity, the other its mass concentration. We compared results for BALP activity and its mass concentration in a group of 88 healthy pre- and postmenopausal women to identify which is a more useful marker for detecting early menopausal bone remodelling changes. METHODS: We measured BALP activity and BALP mass concentration in relation to femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and some other widely used bone markers: osteocalcin (OC), procollagen type I N-terminal propeptide (PINP) and serum C-terminal telopeptide cross-links of type I collagen (CTx) in serum samples from 50 premenopausal (age 45.9+/-4.6 years) and 38 postmenopausal (age 54.4+/-4.5 years) women. RESULTS: Healthy postmenopausal women exhibited 34.2% (p<0.01) and 27.3% (p=0.000) higher levels of BALP activity and mass concentration than premenopausal women, respectively. At the same time, FN and LS BMD were not significantly different between the groups. CTx values were significantly higher in postmenopausal women (p=0.018), while OC and PINP were not. We observed significant correlation between BALP activity and mass concentration (r=0.85, p<0.01). The correlation between BALP activity and FN BMD or LS BMD was insignificant. BALP mass correlated significantly with LS BMD (r=-0.370, p=0.033) but not with FN BMD. As expected, we proved a significant positive correlation for both BALP methods with the other bone markers measured in our study. CONCLUSIONS: Postmenopausal women have slightly higher bone turnover. Since LS and FN BMD were not significantly lower in our group of healthy postmenopausal women, but BALP and CTx were markedly higher, we suggest that measurements of BALP and CTx might be useful as early markers of higher bone turnover. Finally, our results did not show any differences between the clinical utility of BALP activity and BALP mass concentration measurements.     

女性骨生化指标与髋部骨密度的关系

目的探讨血清Ⅰ型胶原N末端肽(sNTX)、血清碱性磷酸酶(sALP)与女性年龄、绝经和髋部骨密度(BMD)之间的关系。方法采用酶联免疫吸附法测定824名20-80岁女性志愿者的sNTX;用全自动生化分析仪测定sALP;采用双能X线骨密度仪测量左髋部BMD。结果(1)sNTX和sALP与年龄呈正相关(r分别为0.333和0.541,P<0.01);在30-39岁年龄段最低,自40-49岁明显升高,与30-39岁年龄段比较有显著差异(P<0.01);两者随年龄的变化以三次回归模型拟合最优(R2分别为0.142和0.343,P=0.000);sNTX和sALP在绝经后较绝经前明显升高,分别达25%和48%。(2)sNTX和sALP与BMD呈显著负相关(r=-0.300--0.492,P<0.01);控制年龄、绝经年限和体重指数后,这种负相关关系仍然存在(P<0.05-0.01);与骨量正常组比较,低骨量组和骨质疏松组妇女的sNTX和sALP显著升高(P<0.01),特别在骨质疏松组升高更显著。结论sNTX和sALP能反映女性随年龄和绝经变化的骨转换状态;高骨转换状态是绝经后女性髋部骨量丢失的重要原因之一。     

Teriparatide (rhPTH 1-34) for the treatment of osteoporosis

Osteoporosis is a skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Osteoporosis develops through an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts resulting in increased bone loss. Numerous agents used for the prevention and treatment of osteoporosis slow bone loss by decreasing both bone resorption and formation. These include bisphosphonates, hormone replacement therapy, selective oestrogen receptor modulators and calcitonins. All reduce vertebral fracture risk and some reduce non-vertebral fracture risk, but none routinely increases bone mass and strength or restores lost bone architecture. In many respects, antiresorptive therapies halt the progression of osteoporosis. However, for patients who have osteoporosis, particularly those who have sustained their first fracture and are at high risk for subsequent fractures, there is a need to develop agents that stimulate bone formation and, thus, reverse osteoporosis. Teriparatide is the recombinant human 1-34 amino acid sequence of parathyroid hormone recently approved in the US for the treatment of men and postmenopausal women at high risk for osteoporotic fracture and in Europe for the treatment of postmenopausal women with osteoporosis. When given by once-daily injection, teriparatide increases bone mass by stimulating formation of new bone, resulting in the restoration of bone architecture.     

Etidronate and alendronate in the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis. DATA SOURCE: A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized. DATA SYNTHESIS: Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate. CONCLUSIONS: No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.     

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     

RISEDRONATE: CLINICAL USAGE

Risedronate is a new bisphosphonate – a family of drugs that inhibit bone resorption – and thus can be used in various bone conditions involving increased levels of bone resorption, such as postmenopausal osteoporosis, glucocorticoid-induced bone loss, and Paget's disease of bone. In placebo-controlled clinical trials, risedronate has been shown to prevent bone loss in postmenopausal women, to decrease the incidence of vertebral and non vertebral (including hip) fractures in postmenopausal women with osteoporosis, and to prevent bone loss in men and women treated with moderate to high doses of glucocorticoids. Risedronate has also been shown substantially to decrease the severity of bone pain and the level of bone turnover in Paget's disease of bone, and to improve the radiographic lesions of this disease. Risedronate is safe and well tolerated. Thus, risedronate is a new option for the management of postmenopausal osteoporosis, Paget's disease of bone and corticosteroid-induced bone loss.     

Bone turnover markers and estradiol level in postmenopausal women.

It has been found recently that women with estradiol (E) levels < 5 pg/ml were more likely to suffer osteoporotic fractures. We evaluated the relationships between biomarkers of bone turnover and changes in hormone levels in early or late postmenopausal women without any replacement therapy. Follicle stimulating hormone (FSH), luteinizing hormones (LH), estradiol and serum resorption (crosslaps) and formation (osteocalcin) markers were assayed. Bone densities in the spine and femoral neck were also measured. Elevated FSH, LH and decreased estradiol in postmenopausal women were accompanied by higher osteocalcin (9.1-9.7 ng/ml) and crosslaps level (3305-3458 pmol/l) compared to premenopausal women (6.8 ng/ml and 2087 pmol/l). Bone density was lower in elderly women. A significant inverse correlation was found between estradiol and crosslaps level; FSH and LH were also correlated with bone markers. Estradiol levels < 9 pg/ml were associated with increased bone resorption, decreased hip bone density and higher frequency of osteopenia and osteoporosis. Over 57% of women with an estradiol < 9 pg/ml could be identified as having "a high turnover" compared with 30% with estradiol above 9 pg/ml. Our results indicate that changes in bone density may not be very clear but an increase in bone turnover is distinctly apparent in women with severe estradiol deficiency.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

骨密度影像学测量与椎体骨折率评估结合提高骨质疏松的诊断率

背景：临床上用于诊断骨质疏松症的通用指标：脆性骨折或骨密度 T ≤-2.5标准差,只要满足一个条件即可作出骨质疏松的诊断。在做骨密度检查时同时进行椎体骨折评估,可以避免单一因素的评判造成骨质疏松症的漏诊,有利于提高骨质疏松的诊断率。目的：评估骨密度结合椎体骨折对骨质疏松症临床诊断率的影响。方法：对217例年龄≥50岁的绝经后女性患者行髋部骨密度检测,同时进行椎体骨折评估,比较单纯依靠骨密度检查与骨密度结合椎体骨折评估对骨质疏松的诊断率的影响,同时探讨骨密度对椎体骨折率的影响。结果与结论：92例骨密度T ≤-2.5,达到骨质疏松诊断阈值,占42.4%;102例骨密度-1〉 T 〉-2.5,为低骨量,占47.0%;23例骨密度在正常范围,骨密度T〉-1,占10.6%。158例无椎体骨折;59例（27.2%）椎体骨折,101个骨折椎。骨密度T〉-2.5的患者椎体骨折率为21.6%,骨密度T ≤-2.5的患者椎体骨折率34.8%,两组骨折率比较差异有显著性意义（P 〈0.05）;骨密度结合椎体骨折评估的骨质疏松诊断率为54.8%,比单纯依靠骨密度检查,骨质疏松诊断率提高12.4%（P=0.01）。说明绝经后女性做骨密度检测的同时进行椎体骨折评估可以提高骨质疏松的诊断率。     

Measuring quality of life with the German Osteoporosis Quality of Life Questionnaire in women with osteoporosis

OBJECTIVE: To evaluate quality of life in women suffering with osteoporosis with or without vertebral fractures for the first time with the German version of the osteoporosis quality of life questionnaire (OQLQ) and to correlate the German OQLQ with the medical outcome survey short-form health survey 36 (MOS SF-36). METHODS: In a cross-sectional study, the OQLQ and the MOS SF-36 were randomly administered to 100 postmenopausal osteoporotic women with a median age of 73.5 (quartiles 65.0; 80.0) years in order to evaluate their quality of life. RESULTS: Of the total number, 56 women had osteoporosis with at least one vertebral fracture and 44 women had osteoporosis without vertebral fracture. All items of the OQLQ as well as the MOS SF-36 showed significantly worse values for the women with vertebral fracture compared to those without vertebral fracture. Both questionnaires' domains evaluating physical wellbeing correlated strongly with each other, supporting the concept of convergent construct validity. The OQLQ domain "emotional function" showed higher correlations with different MOS SF-36 subscores than the MOS SF-36 subscore "role emotional" with the different OQLQ domains. CONCLUSION: The German version of the OQLQ was demonstrated to be feasible. Significantly, worse results in the German OQLQ for postmenopausal osteoporotic women compared to those without vertebral fracture revealed discriminant validity. The disease-targeted OQLQ seems to better reflect problems associated with low emotional wellbeing because of osteoporotic vertebral fracture.