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.     

Vertebral fracture prevalence among women screened for the Fracture Intervention Trial and a simple clinical tool to screen for undiagnosed vertebral fractures. Fracture Intervention Trial Research Group

OBJECTIVE: To evaluate the ability of self-reported risk factors to identify postmenopausal women likely to have extant vertebral fractures because approximately two thirds of women with radiographic evidence of vertebral fracture are unaware of the fracture. PATIENTS AND METHODS: Questionnaire and spinal radiographic data were collected from postmenopausal women with a femoral neck bone mineral density T score of -1.6 or lower during screening for the Fracture Intervention Trial. Logistic regression was used to identify risk factors for extant vertebral fractures and to derive a final multivariable model. RESULTS: Almost two thirds of 25,816 women 55 years and older met the bone density criterion, and 21% of those had an extant vertebral fracture. The final model consisted of 5 self-reported items: history of vertebral fracture, history of nonvertebral fracture, age, height loss, and diagnosis of osteoporosis. These were combined to yield a Prevalent Vertebral Fracture Index (PVFI). The prevalence of women with vertebral fracture varied from 3.8% to 62.3% over the range PVFI of 0 to greater than 5. Among the 13,051 women screened with spinal radiographs, a PVFI of 4 or greater identified 65.5% of women with vertebral fractures (sensitivity), with a specificity of 68.6%. Excluding 881 women who reported prior vertebral fractures reduced the sensitivity to 53.6 % and increased the specificity to 70.7% but did not alter the fracture prevalence at PVFI values less than 6. CONCLUSION: In this population, 5 simple questions identified women who were likely to have undiagnosed vertebral fractures. Further research is needed to determine the validity of this index in other populations, including women without low bone mineral density.     

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.     

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。     

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.     

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.     

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.     

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. Methods: In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS: In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS: s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.     

Broadband ultrasound attenuation in the os calcis: relationship to bone mineral at other skeletal sites

1. We have examined the relationship between broadband ultrasound attenuation in the os calcis and measurements of bone mineral in the distal forearm and lumbar spine of normal and postmenopausal osteoporotic women. 2. Values of broadband ultrasound attenuation in postmenopausal women with vertebral osteoporotic fractures were significantly lower (35%) than in normal pre- and peri-menopausal women (55.4 +/- 3.8 and 79.6 +/- 0.8 dB/MHz, respectively). 3. Broadband ultrasound attenuation correlated significantly with bone mineral content measured in the distal forearm by single-photon absorptiometry (r = 0.77, P less than 0.0001) and with bone mineral content (r = 0.66, P less than 0.0001) and bone mineral density (r = 0.72, P less than 0.0001) measured in the lumbar spine by dual-photon absorptiometry. 4. Although significant, these correlations are not sufficiently close to be predictive. However, the accuracy of broadband ultrasound attenuation in discriminating between normal subjects and patients with vertebral fracture compared very favourably with direct measurements in the spine by dual-photon absorptiometry. 5. Broadband ultrasound attenuation, but not the other measurements, correlated significantly with age in the osteoporotic patients (r = 0.50, P less than 0.05). 6. These findings may reflect the partial dependence of broadband ultrasound attenuation on the intrinsic trabecular architecture of cancellous bone, the disruption of which contributes to an increase in fracture risk.     

Changes in Bone Mineral Density of the Proximal Femur and Spine with Aging: DIFFERENCES BETWEEN THE POSTMENOPAUSAL AND SENILE OSTEOPOROSIS SYNDROMES

We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures. The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged −0.31 (P < 0.05) for the femoral neck, −0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was −1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, “postmenopausal osteoporosis,” is characterized by excessive and disproportionate trabecular bone loss, involves a small subset of women in the early postmenopausal period, and is associated mainly with vertebral fractures. The other form, “senile osteoporosis,” is characterized by proportionate loss of both cortical and trabecular bone, involves essentially the entire population of aging women and, to a lesser extent, aging men, and is associated with hip fractures or vertebral fractures or both.     

Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.     

1,25-Dihydroxyvitamin D stimulation test for osteoblast function in normal and osteoporotic postmenopausal women.

The cause of bone loss in postmenopausal osteoporosis--decreased bone formation or increased bone resorption--is controversial. Synthesis of bone--Gla protein (BGP), a specific osteoblast product, is stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D] in vitro. Thus, increases in serum BGP levels during 1,25(OH)2D administration might provide a useful dynamic index of osteoblast function. We compared 14 postmenopausal osteoporotic women with 12 age-matched postmenopausal normal women before and during 6 d of 1,25(OH)2D administration (2.0 micrograms/d). Serum BGP levels were similar at baseline and increased during treatment in both groups (P less than 0.001). However, trend analysis showed a greater (P less than 0.01) increase in the osteoporotic women. These data do not support the hypothesis that defective osteoblast function is the major cause of bone loss in postmenopausal osteoporosis.     

Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment.

To investigate the effectiveness of calcitonin treatment of postmenopausal osteoporosis in relation to bone turnover, we examined 53 postmenopausal osteoporotic women before and after one year of therapy with salmon calcitonin (sCT), at the dose of 50 IU every other day. Baseline evaluation revealed that 17 (32%) patients had high turnover (HTOP), and 36 (68%) normal turnover osteoporosis (NTOP) as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. The two groups did not differ in terms of bone mineral content (BMC) measured by dual photon absorptiometry at both lumbar spine and femoral diaphysis. However, HTOP patients had higher levels of serum osteocalcin (OC) and urinary hydroxyproline excretion (HOP/Cr). Multivariate regression analysis showed no correlation between parameters of bone turnover (WBR, OC, HOP/Cr) and both femoral and vertebral bone density; the latter being negatively correlated only with the years elapsed since menopause (R2 = 0.406). Treatment with sCT resulted in a significant increase of vertebral BMC in the 53 patients taken as a whole group (+/- 7%, P less than 0.001). When the results obtained in HTOP and NTOP were analyzed separately, only those with HTOP showed a marked increment of spinal BMC (+22%, P less than 0.001), NTOP subjects neither gained nor lost bone mineral during the study. Femoral BMC decreased in the whole group after sCT therapy (-3%, P less than 0.003). However, HTOP patients maintained initial BMC values, whereas those with NTOP lost a significant amount of bone during the study period (-5%, P less than 0.001). The increase of vertebral bone mass was associated with a marked depression of bone turnover detectable in both subsets of patients and in the whole group. In conclusion: (a) assessment of bone turnover cannot help predict the severity of bone loss in postmenopausal osteoporosis; (b) calcitonin therapy appears to be particularly indicated for patients with high-turnover osteoporosis, resulting in a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones.     

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.     

Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss.

Because it is unclear whether age-related bone loss results from increased bone resorption, decreased bone formation or both, we measured the serum level of bone Gla-protein (BGP), a specific marker for bone turnover, in 174 women, ages 30 to 94 yr. Serum BGP increased linearly with aging (r = 0.44, P less than 0.001) from 4.4 +/- 0.4 (mean +/- SE) in the 4th decade to 8.9 +/- 0.9 ng/ml in the 10th decade. This increase correlated inversely (P less than 0.001) with concomitant decreases in bone mineral density at the lumbar spine, midradius, and distal radius. Using partial correlation coefficients, serum BGP still correlated positively with age (r = 0.31, P less than 0.001) after creatinine clearance was fixed but not with creatinine clearance (r = -0.04, NS) when age was fixed. Urinary hydroxyproline (r = 0.29, P less than 0.001), an index of bone resorption, and serum alkaline phosphatase (r = 0.31, P less than 0.001), an index of bone formation, also increased with age and these increases correlated with increases in serum BGP (r = 0.39, P less than 0.001 and r = 0.43, P less than 0.001, respectively). Serum immunoreactive parathyroid hormone concentrations (r = 0.39, P less than 0.001) and urinary cyclic AMP excretion (r = 0.38, P less than 0.001) increased, suggesting that PTH secretion increased with age; these increases correlated significantly with increases in serum BGP. A subgroup of 32 women who were found to have vertebral fractures, hip fractures, or both had significantly higher values for serum BGP than the remainder. These data suggest that overall bone turnover increases in women with aging and, especially considering the concomitant decrease in skeletal mass, do not support the view that age-related bone loss results primarily from decreased bone formation.     

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.     

Pharmacologic therapy for the treatment and prevention of osteoporosis

Clinicians have an expanding menu of attractive pharmacologic options for the prevention and treatment of postmenopausal and age-related osteoporosis. Moreover, there exists excellent data from well-designed clinical trials documenting the effectiveness and tolerability of these therapies. Bone loss can be prevented in postmenopausal women of any age. Fracture risk can be reduced substantially in men and women with previous vertebral fractures or bone density values consistent with osteoporosis. It is clear that therapy is warranted in patients at high fracture risk. Important clinical challenges include devising effective strategies to identify those patients for whom treatment is indicated and to enhance both the accepting and long-term adherence to therapy by patients.     

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     

Clinical sign--height loss and vertebral deformity

Loss of height may be an important clinical sign of vertebral deformation and/or fracture in postmenopausal women and elderly men. The presence of at least one spine fracture will lead to about a 2 cm decrease in height. Guidelines in the U.S. say that height loss greater than 1.5 inches or more from the maximum height among asymptomatic women may be associated with osteoporotic vertebral compression fractures. In Japan, the prevalence of spine deformation starts to increase among individuals in their early 70's, as does the prevalence of those with spine deformation at two or more vertebrae. It has been reported that not only individuals with clinical spine fracture but those with spine deformation show diminished activity of daily living (ADL) and quality of life (QOL) and also high mortality. Spine fracture should be suspected among individuals whose stature has decreased even if they manifest no symptoms.     

Osteoprotegerin serum levels in women: correlation with age,bone mass,bone turnover and fracture status

Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast function and therefore plays an important role in bone remodelling. This study aimed to evaluate the clinical value of serum OPG. Do higher OPG serum levels reflect decreased bone resorption and perhaps higher bone mass in women? Serum OPG levels were measured in 177 healthy women (aged 17-85 years) and in 48 untreated patients (mean age 71 +/- 5) with established osteoporosis, and related to age, bone mass, markers of bone turnover and, in the case of patients with osteoporosis, to pre-existing vertebral fractures. In healthy women OPG levels showed a positive correlation with age (r = 0.25, p < 0.001) but not to bone mass or markers of bone turnover. In women with osteoporosis, however, there was a strong relationship between serum OPG and markers of bone turnover (serum c-terminal crosslinked telopeptides of thpe I collagen (sCTX): r = +0.82, p < 0.0001; osteocalcin (OC): r = +0.69, p < 0.0001), with patients who had higher levels of bone-turnover markers showing higher serum levels of OPG. After adjustment for bone mass and bone markers, patients with pre-existing vertebral fractures had significantly lower serum OPG levels than patients without fractures (57 +/- 8 vs. 97 +/- 10 pg/ml, [mean +/- SE], p < 0.01). The age-dependent increase of OPG as an antiresorptive factor may reflect an insufficient paracrine mechanism of bone cells to compensate for bone loss in older age. In patients with osteoporosis, however, OPG correlated strongly with markers of bone turnover; this may point toward a higher level of RANKL/OPG expression in these patients. Finally, low OPG serum levels seem to be associated with vertebral fractures. We hypothesise that low OPG levels in preset conditions of bone turnover may indicate a higher risk of fracture in patients with osteoporosis.