Mandibular radiomorphometric measurements as indicators of possible osteoporosis in postmenopausal women

OBJECTIVE: The use of mandibular anatomic indicators on panoramic radiographs, i.e. the number of lost teeth, mandibular cortical width at the mental region (MCW), panoramic mandibular index (PMI), alveolar crest resorption degree (M/M ratio) and morphologic classification of the mandibular inferior cortex (MIC grade) can be useful in the evaluation of bone resorption in different age groups of women to determine the presence of osteoporosis. The purpose of this study was to assess the validity of mandibular radiomorphometric measurements and to determine the frequency of tooth loss in postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, MCW, PMI, M/M ratio and MIC grade was performed on dental panoramic radiographs in a group of 133 postmenopausal women 38-80 years-of-age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. RESULTS: In our study when the T-score at the lumbar spine is decreased, the age of menopause is increased, and the MCW is decreased to a point of statistical significance. A decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 43%, having taken into consideration the effect of the years elapsed since menopause. It was also shown that age, years since menopause, MCW value, and the number of teeth lost have a statistically important effect on the incidence of moderate or severe cortical erosion. Moreover, when the MCI is C2 or C3 (mild or severe erosions) the age is increased, the years since menopause are increased and the MCW is decreased to a point of statistical significance. As far as tooth loss is concerned, an increase by 1 unit in the number of teeth lost, increase the likelihood of moderate or severe erosion to 6%, having taken into account the years elapsed since menopause. Our study also demonstrated that postmenopausal women tend to lose their teeth at an age older than 50 years. They usually lose the 1st and 2nd mandibular molars and the 1st and 2nd maxillary premolars. Loss of front teeth and canines occurs at an age older than 60 years (except for the lateral maxillary incisors). At a younger age they tend to lose the 2nd maxillary premolars more frequently than their mandibular counterparts. CONCLUSIONS: In conclusion, panoramic radiographs constitute an integral part of almost every routine dental evaluation and can be useful for the early diagnosis of osteoporosis in postmenopausal women. Dentists have sufficient clinical and radiographic information that enables them to play a significant role in patient screening for osteoporosis.     

Fractal dimension and mandibular cortical width in normal and osteoporotic men and women

Objective

To verify whether fractal dimensions (FD) on the mandibular trabecular and cortical bone and mandibular cortical width (MCW) differ between patients with normal bone mineral density (BMD) and osteoporosis.

Study design

In this retrospective study, 133 dental panoramic radiographs from men aged >60 years and postmenopausal women with a bone densitometry report of the lumbar spine and hip classified as either normal or osteoporotic were selected. Fractal dimensions of five standardized trabecular and cortical mandibular regions of interest and mandibular cortical width were measured on the panoramic radiographs by an experienced oral radiologist, blinded to the densitometric diagnosis. The following statistical analyses were performed: ANOVA and a forward logistic stepwise regression to verify associations between dental panoramic measurements and the densitometric diagnosis. P values less than .05 indicated statistical significance.

Main outcome measures

Fractal dimension and mandibular cortical width.

Results

Differences were found in the FD values on mandibular cortical bone and MCW between patients with normal BMD and with osteoporosis, but not in the FD values of trabecular bone. The odds of having lower mean values of MCW and FD on cortical bone were 2.16, 3125 and 1005 times in osteoporotic patients, respectively, compared with patients with normal BMD.

Conclusion

The values of FD analysis on mandibular cortical bone and MCW were lower in women with osteoporosis. A well-adjusted logistic regression model showed that cortical bone measurements might be considered as auxiliary tools to referring patients for DXA exam.     

Diagnosis of osteoporosis from dental panoramic radiographs using the support vector machine method in a computer-aided system

Background  

Early diagnosis of osteoporosis can potentially decrease the risk of fractures and improve the quality of life. Detection of thin inferior cortices of the mandible on dental panoramic radiographs could be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The aim of our study was to assess the diagnostic efficacy of using kernel-based support vector machine (SVM) learning regarding the cortical width of the mandible on dental panoramic radiographs to identify postmenopausal women with low BMD.     

Serum bone specific alkaline phosphatase and urinary deoxypyridinoline in postmenopausal osteoporosis

The objectives of this study were to: (i) evaluate the diagnostic sensitivity and specificity of the biochemical bone markers: serum total alkaline phosphatase (TALP), bone specific alkaline phosphatase (BSALP) and urinary deoxypyridinoline (Dpyr) in postmenopausal osteoporosis, (ii) compare the bone turnover of postmenopausal osteoporotic patients without and with hormone replacement therapy (HRT) against controls and (iii) identify the correlation between these bone markers and bone mineral density (BMD). We examined 42 postmenopausal women with BMD proven osteoporosis and 35 control subjects. Serum TALP, BSALP and urinary Dpyr were measured. All three biochemical bone markers showed comparable moderate diagnostic sensitivity but Dpyr had the highest diagnostic specificity. There were significantly higher serum TALP, BSALP and urinary Dpyr levels in non-HRT treated patients compared to controls (p<0.005, <0.0001 and <0.005 respectively). There were no significant differences in the levels of all three bone markers between HRT treated patients and control subjects. There was no significant correlation between TALP, BSALP or Dpyr and BMD in both controls and patients. In conclusion, the biochemical bone markers are not useful in diagnosis of postmenopausal osteoporosis but may have a role in monitoring progress and response to treatment. HRT treatment reduces bone turnover of postmenopausal osteoporosis.     

Identification of the risk factors for osteoporosis among postmenopausal women

ObjectivesThe aim of this study was to determine the effect of different durations of menopause at the time of bone mineral density (BMD) measurement and of different age at menopause intervals on the prevalence of osteopenia and osteoporosis among untreated postmenopausal women. We also assessed related factors leading to low BMD.MethodsA total of 2769 postmenopausal women who had not taken any anti-osteoporosis treatment and/or hormone replacement therapy were divided into three groups according to duration of menopause at the time of BMD measurement. The women were also evaluated in four different age groups according to their age at menopause onset. Multinomial logistic regression analysis was used to determine related factors leading to low BMD. Investigated parameters include demographic characteristics, plasma glucose, lipids, and lipoproteins.ResultsAccording to World Health Organization (WHO) criteria, among 2769 patients, 449 (16.2%) were identified as having osteoporosis, 1085 (39.2%) as having osteopenia, and 1235 (44.6%) as having normal BMD. Osteoporosis was determined in 10.6% and 16.2% of women with menopause duration of 0–3 years and 4–7 years, respectively, whereas this rate was 31.9% in women with menopause duration of over 7 years (p = 0.001). The percentages for osteopenia remained constant among the three different menopause durations (0–3 years: 37.2%, 4-7 years: 42.1%, and >7 years: 40.9%). Thirty percent of women with age at onset of <40 years were osteoporotic. However, the percentages of women with osteoporosis among the other age groups were similar (40–46 years: 18.3%, 47–52 years: 14.1%, and >52 years: 15.4%). The percentages for osteopenia remained relatively constant among the four age groups (36.7, 40, 39.1 and 39%). According to the multinomial logistic regression analysis, duration of menopause at the time of BMD test and parity were positively correlated with both osteoporosis and osteopenia, while glucose level was negatively correlated with both osteoporosis and osteopenia. Age at menopause was negatively correlated only for osteoporosis. Low-density lipoprotein cholesterol (LDL-c) level may be accepted as a clinically significant factor for osteopenia (OR: 1.01; CI_95%: 1.00–1.02). No differences were determined in the prevalence of osteopenia and osteoporosis in women with menopause duration of >7 years when evaluated according to the four menopause age groups as described before (p = 0.74). Contribution to the regression model was 0.8% by age at menopause, 5.6% by menopause duration at time of BMD measurement, 5.8% by both factors.ConclusionAccording to our results, osteoporosis is related more to the duration of menopause at the time of BMD measurement rather than the age at menopause among untreated postmenopausal women. High parity was determined as another risk factor for low BMD.     

Bisphosphonates for prevention of postmenopausal osteoporosis

Our studies showed that 5 mg alendronate per day was the lowest, most effective dose that persistently prevented bone loss in recently postmenopausal women with normal bone mass. The effect on bone mass and biochemical markers was found comparable to that of commonly recommended regimens of postmenopausal HRT, and 5 mg alendronate per day is suggested as a new option for prevention of postmenopausal osteoporosis. HRT must, however, still be considered the first choice for this indication because of additional beneficial effects on other organ systems. The effect of alendronate was unaffected by bone or fat mass status, but increased with increasing postmenopausal age. The implications were that alendronate stabilized bone mass to a comparable extent in women at particular risk of osteoporosis because of thin body habitus or low bone mass and in healthy postmenopausal women with normal bone mass. Calcium supplementation was insufficient to prevent bone loss and did not add an effect on bone metabolism when combined with alendronate treatment in recently postmenopausal women. The gastrointestinal risk and adverse event profile of 5 mg alendronate per day was comparable to that of placebo, and this dose of alendronate appeared safe for long-term use. Bone loss resumed at a normal postmenopausal rate promptly after withdrawal of alendronate in early postmenopausal women consistent with a substantial underlying natural bone loss during early menopause. Oral ibandronate increased bone mass at all skeletal regions in elderly postmenopausal women with low bone mass, and 2.5 mg ibandronate per day was the lowest dose with this effect. The results are indicative of ibandronate as an option for secondary prevention of postmenopausal osteoporosis, but longer-term phase III trials should be performed before ibandronate can be recommended for this indication. The study showed that 2.5 mg ibandronate per day was efficient for prevention of bone loss and increment in bone mass in a population of women at particular risk of osteoporosis because of low bone mass. There were no differences between 2.5 mg ibandronate per day and placebo in terms of side effects, including complaints from the gastrointestinal tract, and ibandronate appeared safe for longer-term use in this dosing. Bone loss resumed at a normal postmenopausal rate when treatment was withdrawn. The response in bone mass and biochemical markers indicated that 2.5 mg ibandronate per day is equivalent to 10 mg alendronate per day in postmenopausal women. Our studies of two recently developed biochemical markers, urine CTX and serum total OC, showed that bone turnover was lowest in the premenopausal period, where these biochemical markers furthermore revealed a negative association with bone mass. It indicated that increased bone turnover contributes to a small premenopausal bone loss and resulting lowered bone mass. In consistence, a small premenopausal bone loss was observed in some regions of the hip. The biochemical markers increased at the time of menopause, consistent with initiation of the postmenopausal bone loss, and became gradually more negatively associated with bone mass as time past the menopause increased. The biochemical markers were furthermore higher in postmenopausal women with low bone mass, consistent with the characterization of postmenopausal osteoporosis as a condition with increased bone turnover. Our results consistently indicated a central role of increased bone turnover for development of low bone mass and osteoporosis. It is, however, also important to stress that the associations between biochemical markers and bone mass were too weak to allow for a valid individual estimation of bone mass based on biochemical markers. In contrast, the biochemical markers were shown as valid tools for monitoring and prediction of treatment effect of bisphosphonates. CTX, NTX, and total OC revealed the best performance characteristics in this respect. Six months after start of treatment, the level of suppression of these biochemical markers of bone resorption and formation accurately reflected the size of the 1-2 year response in bone mass in groups of women treated with bisphosphonate. This was a clear advance over bone densitometry, which has a precision error in the area of the anticipated yearly bone mass response during bisphosphonate therapy. The relationship was consistent during treatment with alendronate or ibandronate and in younger or elderly postmenopausal women. In individual patients, cut-off values of an about 40% decrease in urine CTX or NTX and an about 20% decrease in total OC validly predicted long-term prevention of bone loss. The sensitivity of prediction was high, but the specificity low. This implicated that the biochemical markers could be used as an exact method to detect "responders" to therapy, whereas "non-responders" to bisphosphonate treatment should be detected with bone densitometry in patients who do not reveal a decrease below the cut-off value in the biochemical marker during treatment. However, before such approach can be generally recommended the cut-off values of the biochemical markers should be validated in future clinical trials of bisphosphonate. Postmenopausal osteoporosis develops slowly over many years and mainly becomes a significant individual and socio-economic health problem 1-3 decades after the menopause. Prevention of postmenopausal osteoporosis by bisphosphonates is therefore likely to imply a treatment regimen of at least a decade, as presently recommended for HRT (Consensus Development Statement 1997). However, future cost-effectiveness studies should reveal when bisphosphonate treatment should ideally be initiated. Our studies showed that the bisphosphonates were effective over the range from general recommendation (recently postmenopausal women with normal bone mass) to a reservation for women at particular risk of osteoporosis (elderly women, thin women, or women with osteopenia). Presently available biochemical markers could be used for groupwise and individual monitoring and prediction of treatment response. Most presently available biochemical markers, however, have the drawback of a low specificity. Recent studies of CTX measured in serum are promising, and indicate that this new biochemical marker might have overcome these drawbacks due to a pronounced response to treatment and a low long-term biological variation (Christgau et al. 1998b, Rosen et al. 1998, and 2000).     

Bone turnover biomarkers in obese postmenopausal Saudi women with type-II diabetes mellitus

BackgroundThere is a high prevalence of diabetes mellitus type-2 (T2DM) and osteoporosis are problems worldwide. In this study, we evaluated the correlation between T2DM and bone turnover in diabetic obese postmenopausal Saudi women.ResultsSerum OC levels were significantly decreased in diabetic obese postmenopausal group compared to their respective healthy group (P < 0.004). PICP and Cath K were significantly elevated in diabetic postmenopausal group compared to the healthy group (P < 0.024 & 0.001). A significant elevation in 1,25(OH)2 Vitamin D3, Ca and Pi levels in diabetic obese postmenopausal patients group compared to the healthy group. However, a non-significant changes was observed in serum PTH level between different groups.ConclusionIn this study, the changes in the biochemical parameters and bone turnover markers in obese women are strong risk factors for diabetes development that may contribute to osteopenia and osteoporosis. The study showed the strong effect of T2DM on biochemical markers of bone turnover in obese postmenopausal Saudi women.     

Multiparameter analysis of serum levels of C-telopeptide crosslaps,bone-specific alkaline phosphatase,cathepsin K,osteoprotegerin and receptor activator of nuclear factor κB ligand in the diagnosis of osteoporosis

ObjectivesC-telopeptide crosslaps (CTX) and bone-specific alkaline phosphatase (BAP) do not provide sufficient sensitivity and specificity for diagnosis of osteoporosis. Cathepsin K (CatK), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (total (t) and soluble (s) RANKL) play an important role in bone metabolism. Thus serum levels of biochemical markers, each or in combination, may be useful in diagnosis of osteoporosis.Study DesignIn total, 121 healthy women, 27 premenopausal women aged between 20 and 45 years, and 94 postmenopausal women aged 59–81 years, all free of known skeletal disorders were included. They underwent bone density measurement and measurement of biochemical markers.Main Outcome MeasuresBased on WHO criteria, women were stratified in four groups (premenopausal: healthy; postmenopausal: healthy, osteopenia, osteoporosis), and their levels of CatK, OPG, RANKL, CTX and BAP were analyzed.ResultsUsing WHO criteria 21 postmenopausal women had normal bone mineral density (BMD), 49 had osteopenia and 24 had osteoporosis. There were no significant correlations of CatK, OPG and RANKL with BMD (T-score) in age-adjusted analysis, but for BAP and CTX. ROC analyses resulted in poor diagnostic validity of all parameters. The best result – also confirmed by discriminant analysis – was yielded by BAP (AUC = 0.646 [0.510; 0.781]). A combination of variables did not significantly improve the diagnostic power.ConclusionsBaseline serum levels of BAP, CTX, CatK, OPG, sRANKL or tRANKL alone or in combination are not suitable to distinguish osteoporotic from non-osteoporotic postmenopausal women with sufficient accuracy.     

Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis

Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis.Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia.Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score.Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis.     

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

Biochemical markers of bone turnover : clinical usefulness in osteoporosis

The recent development of specific and sensitive biochemical markers reflecting the overall rate of bone formation and bone resorption, has markedly improved the non invasive assessment of bone turnover in various metabolic bone diseases, especially for osteoporosis. The immunoassay of human osteocalcin recognizing the intact molecule and its major proteolytic fragment, assays for bone alkaline phosphatase and the intact form of the N-terminal extension propeptide of type I collagen are currently the most sensitive markers to assess bone formation. The best indices of bone resorption are the new immunoassays for the pyridinoline crosslinks and type I collagen related peptides in urine, but also very recently available in serum. Using these new markers, several studies have shown that bone turnover increases markedly after the menopause and remains elevated in late postmenopausal and elderly women. An increased bone turnover rate is related to a fast rate of bone loss in postmenopausal women and to a decreased bone mass in elderly women. Recent data suggest that some of the new immunoassays for pyridinoline crosslinks and related peptides could predict the subsequent risk of hip fracture in elderly women. Thus, bone markers might be used in combination with bone mass measurement to improve the prognostic assessment of postmenopausal women, i.e. their risk of developing osteoporosis and ultimately fractures. Treatment of postmenopausal women with antiresorptive drugs such as estrogens, bisphosphonates and calcitonin is followed by rapid decrease of the levels of bone markers that is correlated with the long term increase of bone mass as assessed by dual-energy X ray absorptiometry measurement. Thus, bone markers should be useful in monitoring treatment efficacy in patients with osteoporosis. Appropriate combination of the most efficient markers of bone formation and resorption will probably provide a powerful tool in the clinical investigation of osteoporosis.     

Relationship between blood pressure levels and bone mineral density in postmenopausal Turkish women

Introduction

We investigated the association between bone mineral density (BMD) detected by dual-energy X-ray absorptiometric (DXA) method and blood pressure (BP) in a large sample of postmenopausal women.

Material and methods

The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 ±8.8 years, who were screened for osteopenia or osteoporosis by DXA. Patients with hypertension (HT, n= 306) were compared with normotensive (NT, n = 290) individuals. Bone mineral density results for the femur neck and spine were classified into 3 groups according to World Health Organization criteria: normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD) and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were grouped as having low bone mass (LBM).

Results

There were no significant differences in femur T score, femur BMD, femur Z score, spinal T score, spinal BMD and spinal Z score between hypertensive and normotensive groups. The group of patients with low bone mass calculated from femur T scores had higher age, systolic BP, duration of hypertension and duration of menopause, but lower BMI. Similarly, patients with low spine BMD had higher age and duration of menopause, but lower BMI. Linear regression analysis showed a significant correlation between systolic BP and femur BMD and T score values. Furthermore, logistic regression analysis revealed that hypertension is an independent predictor of spinal osteopenia and osteoporosis.

Conclusions

The presence of hypertension is an independent predictor of spinal low bone density in Turkish women after menopause.     

Peripheral quantitative computed tomography (pQCT) is useful for monitoring bone mineral density of the patients who receive hormone replacement therapy

OBJECTIVE: A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). METHODS: Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. RESULTS: The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION: Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.     

Spotlight on Denosumab in Postmenopausal Osteoporosis

Denosumab (Prolia®) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU, and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function, and survival. In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral, and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established. Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.     

Treatment of osteoporosis with denosumab

Osteoporosis is a common skeletal disease associated with an imbalance in bone remodeling resulting in a reduction in bone strength and increased fracture risk. The principal regulator of osteoclastic bone resorption is receptor activator of nuclear factor-κB ligand (RANKL), a cytokine member of the tumor necrosis factor family. The binding of RANKL to its receptor on the cell surface of osteoclasts and pre-osteoclasts increases the formation, activity, and survival of osteoclasts. Denosumab is an investigational fully human monoclonal antibody to RANKL. By binding to RANKL, denosumab prevents RANKL from binding to its receptor, resulting in a decrease in bone resorption due to reduction in the formation, activity, and survival of osteoclasts. In postmenopausal women with osteoporosis, denosumab 60 mg by subcutaneous injection every 6 months increased bone mineral density (BMD), reduced bone turnover markers, and reduced the risk of vertebral, hip, and non-vertebral fractures. In postmenopausal women with low BMD, denosumab increased BMD and reduced bone turnover markers. It was well tolerated with a safety profile generally similar to placebo. Denosumab is a promising emerging drug for the prevention and treatment of postmenopausal osteoporosis. It may be particularly useful in clinical practice for the treatment of patients with gastrointestinal contraindications or side effects with oral bisphosphonates and for patients with malabsorption.     

Soy isoflavones for osteoporosis: an evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.     

The effect of tibolone on bone mineral density in postmenopausal women with osteopenia or osteoporosis--8 years follow-up

OBJECTIVES: This longitudinal observational study evaluated the effect of 8 years of uninterrupted treatment of tibolone on bone mineral density (BMD) in postmenopausal women with significant osteopenia or osteoporosis. MATERIAL AND METHODS: Subjects were 66 postmenopausal women (29 with moderate or severe osteopenia and 37 with osteoporosis) who took tibolone (2.5 mg nocte) uninterruptedly for over 8 years and who attended for annual BMD assessments. Their mean age was 66.7 (0.86) years (range 50-86 years). BMD measurements at the lumbar spine and proximal femur were performed annually by dual-energy X-ray absorptiometry (DEXA). RESULTS: During the 8 years of treatment with tibolone there was a significant increase in BMD at the spine (P < 0.001) and at the hip (P < 0.001). Women who did not have previous oestrogen therapy had significantly greater response to tibolone than those who had previous treatment with conventional hormone replacement therapy (HRT). CONCLUSION: This long-term observational study provides evidence of the effectiveness of tibolone in postmenopausal women with moderate/severe osteopenia and osteoporosis in terms of a significant increase in BMD.     

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized,Double-Blind,Placebo-Controlled Trial with Open-Label Extension

PurposeThe efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study.ResultsBaseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals.ConclusionDenosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.     

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

Purpose

The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Materials and Methods

One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 µg daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period.

Results

Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months).

Conclusion

The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.