Osteopenic Women Research Articles

Clinical and radiographic evaluation of effect of risedronate 5 mg as an adjunct to treatment of chronic periodontitis in postmenopausal women (12-month study)

Bisphosphonates are beneficial to women, after menopause, in treatment of gum diseases. In this study, significant improvement in the disease condition was found and that no further progress was noted, and no side effects were reported. Bisphosphonates can be safely and successfully be used to support oral health procedures. The purpose of this study was to evaluate host modulating effect of bisphosphonate adjunct with the treatment of chronic periodontitis in osteopenic and osteoporotic postmenopausal women. Twenty-two osteopenic and osteoporotic postmenopausal women with moderate to severe chronic periodontitis were selected for the study. On intraoral examination, periodontal parameters like probing depth (PD), clinical attachment level (CAL), Plaque Index (PI) and Gingival Index (GI) were recorded. Scaling and root planing were done. Intraoral periapical X-rays were taken, and alveolar bone density (ABD) was measured with cone beam computed tomography (CBCT), and then, medications (risedronate 5mg once daily (OD), calcium citrate 250mg OD, vitamin D 400IU OD) were given. Patients were recalled for follow-up at 3, 6 and 12months. Intraoral periapical (IOPA) X-rays were taken at 6 and 12months and ABD was measured at baseline and 12months. There was a significant improvement in all the parameters. There was an increase of 0.02 ± 0.001cm on CT scan and 0.38 ± 0.005mm on IOPA in bone height over 12months from baseline. Bone density increased by 118.56 ± 3.251 Hounsfield units (HU). There was no progress in the disease, and further bone loss was not noticed. This is in correlation with clinical parameters which showed highly significant gain in CAL (3.57 ± 0.234mm) and reduction in PD (2.20 ± 0.229mm) Bisphosphonate therapy as an adjunct to scaling and root planing may have significant beneficial clinical effects on the periodontium of postmenopausal women with moderate to severe chronic periodontitis.

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

We used two methods of identifying women who reached the target for raloxifene treatment with bone turnover markers. Both approaches identified women that responded to treatment but did not fully agree and may be complementary. The change in bone turnover markers (BTMs) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Fifty postmenopausal osteopenic women (age 51-72years) were randomised to raloxifene or no treatment for 2years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40years). Bone mineral density (BMD) was measured at the spine and hip. There was a decrease in BTM in response to raloxifene treatment, percentage change at 12weeks: C terminal telopeptide of type I collagen (CTX) -39% (95% CI -48 to -28) and N terminal propeptide of type I procollagen (PINP) -32% (95% CI -40 to -23) P < 0.001. The proportion of women classified as responding to treatment using LSC at 12weeks was as follows: CTX 38% and PINP 52% and at 48weeks CTX 60% and PINP 65%. For the RI approach, the proportion of women classified as responding to treatment at 12 weeks was CTX and PINP 38 % and at 48 weeks CTX 40% and PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene-treated group compared to the no-treatment group at week 48: difference 0.031g/cm(2) (95% CI 0.016 to 0.046, P < 0.001). The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response, but the two approaches do not fully overlap and may be complementary.

The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial.

Daily consumption of 50g of dried plum (equivalent to 5-6 dried plums) for 6months may be as effective as 100g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. To some extent, these results may be attributed to the inhibition of bone resorption with the concurrent maintenance of bone formation. The objective of our current study was to examine the possible dose-dependent effects of dried plum in preventing bone loss in older osteopenic postmenopausal women. Forty-eight osteopenic women (65-79years old) were randomly assigned into one of three treatment groups for 6months: (1) 50g of dried plum; (2) 100g of dried plum; and (3) control. Total body, hip, and lumbar bone mineral density (BMD) were evaluated at baseline and 6months using dual-energy X-ray absorptiometry. Blood biomarkers including bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP-5b), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin were measured at baseline, 3months, and 6months. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6months. Both doses of dried plum were able to prevent the loss of total body BMD compared with that of the control group (P < 0.05). TRAP-5b, a marker of bone resorption, decreased at 3months and this was sustained at 6months in both 50 and 100g dried plum groups (P < 0.01 and P < 0.04, respectively). Although there were no significant changes in BAP for either of the dried plum groups, the BAP/TRAP-5b ratio was significantly (P < 0.05) greater at 6months in both dried plum groups whereas there were no changes in the control group. These results confirm the ability of dried plum to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50g) may be as effective as 100g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. This clinical trial was registered at ClinicalTrials.gov: NCT02325895 .

Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T-Score: An International Multicenter Study

Because single-center studies have reported conflicting associations between microarchitecture and fracture prevalence, we included high-resolution peripheral quantitative computed tomography (HR-pQCT) data from five centers worldwide into a large multicenter analysis of postmenopausal women with and without fracture. Volumetric BMD (vBMD) and microarchitecture were assessed at the distal radius and tibia in 1379 white postmenopausal women (age 67 ± 8 years); 470 (34%) had at least one fracture including 349 with a major fragility fracture. Age, height, weight, and total hip T-score differed across centers and were employed as covariates in analyses. Women with fracture had higher BMI, were older, and had lower total hip T-score, but lumbar spine T-score was similar between groups. At the radius, total and trabecular vBMD and cortical thickness were significantly lower in fractured women in three out of five centers, and trabecular number in two centers. Similar results were found at the tibia. When data from five centers were combined, however, women with fracture had significantly lower total, trabecular, and cortical vBMD (2% to 7%), lower trabecular number (4% to 5%), and thinner cortices (5% to 6%) than women without fracture after adjustment for covariates. Results were similar at the radius and tibia. Similar results were observed with analysis restricted to major fragility fracture, vertebral and hip fractures, and peripheral fracture (at the radius). When focusing on osteopenic women, each SD decrease of total and trabecular vBMD was associated with a significantly increased risk of major fragility fracture (OR = 1.55 to 1.88, p < 0.01) after adjustment for covariates. Moreover, trabecular architecture modestly improved fracture discrimination beyond peripheral total vBMD. In conclusion, we observed differences by center in the magnitude of fracture/nonfracture differences at both the distal radius and tibia. However, when data were pooled across centers and the sample size increased, we observed significant and consistent deficits in vBMD and microarchitecture independent of total hip T-score in all postmenopausal white women with fracture and in the subgroup of osteopenic women, compared to women who never had a fracture. © 2016 American Society for Bone and Mineral Research.

Influences of teriparatide administration on marrow fat content in postmenopausal osteopenic women using MR spectroscopy

Objective Teriparatide could induce osteoblast differentiation of mesenchymal stem cells while inhibiting adipocyte differentiation. However, there are significant differences between ex vivo and in vivo models. We aimed to evaluate the impact of teriparatide on marrow and abdominal fat accumulation in postmenopausal osteopenic women.Methods Postmenopausal osteopenic women were randomly assigned to receive teriparatide or placebo for 12 months. Subcutaneous (SAT) and visceral adipose tissue (VAT), marrow fat fraction (MFF), bone density (BMD) and bone biomarkers were measured at baseline, 6 and 12 months.Results At 12 months, mean percentage changes in BMD from baseline were 3.51%, 2.21% and 1.80% at lumbar spine, total hip and femoral neck for the teriparatide group, respectively. Relative to baseline conditions, teriparatide reduced MFF (–3.54% at 6 months; –5.87% at 12 months, all p < 0.01). A significant difference in MFF, but not BMD, was first detected at 6 months (p = 0.012) between groups. MFF was negatively associated with SAT (r = –0.479) and positively associated with VAT (r = 0.531) and VAT/SAT (r = 0.415, all p < 0.05). Teriparatide treatment did not alter abdominal fat composition.Conclusion Teriparatide effectively lowers marrow adiposity but not abdominal fat accumulation in postmenopausal osteopenic women.

An evaluation of homocysteine, C-reactive protein, lipid levels, neutrophils to lymphocyte ratio in postmenopausal osteopenic women

Objective: In the present study, the risk coefficients of serum homocysteine (hcy), lipid levels, C-reactive protein (CRP), neutrophils to lymphocyte ratio (NLR) in postmenopausal osteopenic women were determined.Methods: We enrolled 269 patients with postmenopausal women from Hangzhou No.1 Hospital gynecological clinic, who aged 45 to 60 years old and never received menopause hormone therapy. According to the bone mineral density determination results, subjects were divided into normal group (n = 128), osteopenia group (n = 141). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). Serum hcy, CRP and lipid indexes were determined by enzyme chemiluminescence immunoassay.Results: The odds ratios (OR) and 95% confidence intervals (CI) of those variables (menopausal age, duration of menopause, LDL, CRP, hcy and NLR) were found significant (p < 0.05). Menopausal age, duration of menopause, LDL, CRP, hcy and NLR variables were found statistically significant in the analysis of receiver operating characteristic (ROCs).Conclusion: The present study shows that menopause age, duration of menopause, serum LDL, CRP, hcy and NLR levels are risk factors for postmenopausal osteopenic women, which may be used as the indicators of bone loss in postmenopausal women.

Bone Marrow Lipid Profiles from Peripheral Skeleton as Potential Biomarkers for Osteoporosis: A 1H-MR Spectroscopy Study

To characterize the lipidic profile of bone marrow in the calcaneus and femoral neck of healthy, osteopenic, and osteoporotic women, by using magnetic resonance spectroscopy (MRS) at 3T. The final goal was to identify specific metabolites with the potential ability to discriminate between healthy, osteopenic, and osteoporotic subjects. Sixty-two and thirty three postmenopausal women recruited to investigate calcaneus and femoral neck, respectively, underwent a bone mineral density (BMD) measurement to be classified as healthy subjects (n = 22), osteopenic (n = 45), or osteoporotic (n = 28) patients. MRS spectra were used to quantify and compare bone marrow fat resonances between the three BMD groups. Between-group differences were tested using a Welch analysis of variance. Multiple comparisons were made with the Games-Howell correction. Relationships between pairs of variables were assessed with linear correlation analysis. Reproducibility analysis was performed for all the lipid resonances in both sites. The reproducibility was satisfactory. In femoral neck, methylene (L13), glycerol (L41, L43), and total lipid resonances were significantly lower in healthy as compared to osteoporotic subjects. On the other hand, in calcaneus, L13/glycerol significantly discriminated between osteopenic and osteoporotic subjects whereas L13/(unsaturated lipid) discriminated between healthy and osteopenic group. However, the reproducibility of both unsaturated lipid and glycerol resonances were less optimal. MRS of bone marrow lipid profiles from peripheral skeletal sites may be a promising tool for screening of large population to identify individuals with or at risk for developing osteoporosis. Moreover, it provides information about the metabolic changes occurring in bone marrow with the development of osteoporosis, which are skeletal site dependent.

Accuracy of a fracture risk assessment tool in Iranian osteopenic and osteoporotic women

Objective: Bone mineral densitometry (BMD) has been well known as a practical method in the detection of osteoporosis. However, it is not accurate in the identification of fracture risk in non- osteoporotic patients because of its low sensitivity. Fracture Risk Assessment Tool (FRAX) is a sensitive WHO recommended risk assessment tool for the prediction of the risk of fracture in order to diagnose patients who would benefit the most from pharmacological treatment. Methods: This cross-sectional study included a sample of 361 Iranian women aged 40 to 80 years- old who, for any reason, were referred for humeral BMD. Femoral BMD and FRAX were performed on all of the subjects and the results were compared to one another to figure out the accuracy of FRAX to detect the patients at high risk of fracture. Results: There were 361 participants in the study with a mean age of 56.4 ± 5.5 years, and comprised of 89 (24.7%) osteoporotic (T-score -2.5), 125 (34.7%) osteopenic (T-Score between -1 and -2.5) and 147 (40.7%) subjects with T-score > -1. A 10-year probability of hip fracture of more than 3% was detected in only in six women (1.6%) and a major osteoporotic fracture risk (of higher than 20%) was not detected in any subject. Conclusion: Applying FRAX in osteopenic and osteoporotic Iranian women showed no extra benefit in comparison to using BMD alone. It seems that FRAX is not accurate in our population as it underestimates the number of patients that could benefit from osteoporosis treatment.

Awareness of osteoporosis in postmenopausal Indian women: An evaluation of Osteoporosis Health Belief Scale.

Context:The level of awareness about osteoporosis in postmenopausal women who are the common sufferers.Aims:This study aims to evaluate the level of awareness in postmenopausal women using the Osteoporosis Health Belief Scale (OHBS).Settings and Design:Osteoporosis has emerged as a common health problem in geriatric population. A proactive role needs to be played for preventing its consequences. Before initiating any preventive measures, an evaluation of awareness level of the target population is necessary. The questionnaire-based study design was used for this study.Subjects and Methods:A questionnaire (OHBS)-based study in 100 postmenopausal women in Chandigarh was conducted. The bone mineral density (BMD) was measured in each case by dual energy X-ray absorptiometry. Height, weight, and body mass index (BMI) of the participants were noted.Statistical Analysis Used:Statistical analysis was conducted to evaluate any correlation between the various components of the OHBS and the BMD.Results:No statistically significant difference was noted in the seven component parameters of OHBS among the normal, osteopenic, and osteoporotic women suggesting that the health belief regarding susceptibility is not much different between the three groups of the study population. A statistically significant difference between the mean BMI of normal and osteoporotic population was noted.Conclusions:The results show that there is a great deficit in the awareness level of postmenopausal Indian women regarding osteoporosis. Most of the women were unaware of the condition and the means to prevent it. The study emphasizes that health care professionals have lot of ground to cover to decrease the incidence of osteoporosis and its associated health problem.

Evaluation of the quality of life of postmenopausal osteoporotic and osteopenic women with or without fractures.

IntroductionMost studies concerned with the quality of life (QoL) of women with reduced bone mineral density (BMD) focus on patients with vertebral and non-vertebral fractures. Our objective was to evaluate QoL among patients with reduced BMD regardless of their fracture history compared to women with normal BMD.Material and methodsEighty-five patients in the study group were classified as osteoporotic, with BMD results measured by densitometry and expressed by T-score ≤ –2.5 SD, 122 women were osteopenic, with –2.5 < T-score ≤ –1.0 SD, and 97 subjects were assessed as normal, with T-score > –1.0 SD. Mean ages of women according to groups were 59.90, 57.67 and 55.68, respectively. Assessment of life quality was conducted using the Polish version of the QUALEFFO-41 scale.ResultsThe ratings in the assessment (QUALEFFO-41) of QoL were lower for osteoporotic and osteopenic women than for the normal BMD group with regard to pain (p = 0.006), social function (p = 0.001), health perception (p = 0.001), and mental function (p = 0.001). For total QUALEFFO-41 the associated factors were: secondary and higher education (OR = 0.49; 95% CI: 0.29–0.82), self-perceived deformity of the back (OR = 4.09; 95% CI: 1.88–8.93), previous fractures (OR = 2.52; 95% CI: 1.09–5.82), reduced height (OR = 2.48; 95% CI: 1.13–5.39) and anxiety (OR = 1.42; 95% CI: 1.21–1.66).ConclusionsIt seems necessary to evaluate QoL of women with reduced BMD before fractures occur, to aid development of health education aiming to reduce the incidence of osteoporosis and prevent fractures.

Isokinetic adaptations of knee extensors and flexors after aerobic walk training in old sedentary women

We examined the effects of active walk training 3 days per week, for 24 weeks on isokinetic peak torque (PT) and mean power (MP) of the knee extensors and flexors of osteopenic sedentary old women. The population was composed by 121 women (65.5 ± 4.2 years) with 5.3 (± 1.7) to the Physical Activity Scale for the Elderly (PASE) and 86% of the theoretical distance of the 6-minute walk test (6MWT). The women were eligible to participate if they had no medical contraindication and were not diagnosed with major motor and neurocognitive dysfunctions. The isokinetic performance of the knee extensors and flexors in both limbs was measured on Biodex System 3 ® in concentric/concentric condition on 80° range of motion. The experimental protocol consisted in 5 maximal effort performed at 60°/sec, 60 second of rest interval and 5 maximal effort at 180°/sec. After 5 minutes of rest, identical paradigm was performed on contro-lateral side. Experimental group performed aerobic walk training: (1) between 60 and 80% of maximal heart rate; (2) with a distance between 1500 to 4500 meters at the end of the training; (3) with a total time effort between 25 to 45 minutes at the end of the training. Our results showed significant increase of PT of hamstring in dominant side at 180°/sec ( p < 0.01). We observed significant differences in the experimental group for the hamstring at 60°/sec for the dominant side ( p < 0.02) and the no-dominant side ( p < 0.01). For MP, no interaction was observed between groups and time. For the hamstring, we observed significant increase in the experimental group at 60°/sec on the no-dominant side ( p < 0.05). Our results indicate a moderate effects of the aerobic walk training performed during 6 months on the peak torque and the mean power of isokinetic knee extensors and flexors in old sedentary women.

Effects of strontium ranelate on markers of cardiovascular risk in postmenopausal osteoporotic women.

Recent pooled analyses have shown that strontium ranelate increases the incidence of venous thromboembolism and non-fatal myocardial infarction, but no explanations were given. The aim of our study was to assess the effects a 12-month treatment with strontium ranelate on hemostasis factors and markers of cardiovascular risk in postmenopausal osteoporotic women. Forty osteoporotic postmenopausal women received orally strontium ranelate 2g daily, plus calcium and colecalcipherol for 12months. Forty postmenopausal osteopenic women matched for age, menopausal age, and body mass index served as controls and received orally calcium and colecalcipherol for 12months. Biochemical cardiovascular risk factors and hemostatic indices were assayed prior to treatment, and after 3, 6, and 12months of therapy. These indices included fibrinogen, fasting glucose, total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, plasma levels of D-dimer, homocysteine, partial thromboplastin time, and prothrombin time. In addition, we evaluated possible changes in blood pressure and occurrence of venous thromboembolic events. At baseline, no statistically significance was observed between the two groups except for bone mineral density at lumbar spine, femoral neck, and total femur, which was lower in strontium ranelate group. After 12months of treatment, there was no statistically significant change in cardiovascular risk factors and hemostatic parameters. None of the 40 women developed any clinical venous thromboembolic event. A 12-month treatment with strontium ranelate did not alter hemostasis factors or markers of cardiovascular risk, suggesting that reported increased risk of venous thromboembolism and myocardial infarction with strontium is mediated by other factors.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

PurposeCollagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.MethodsForty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.ResultsOVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.ConclusionsOur data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Long-Term Exercise and Bone Mineral Density Changes in Postmenopausal Women--Are There Periods of Reduced Effectiveness?

There is increasing evidence that physical exercise can prevent fractures in postmenopausal women. However, even with careful adaptation of the exercise program to subjects' changing bone, health, and fitness status, effectivity may still decrease over the time. This could be specifically the case where the limitations of higher age collide with the specification of the exercise program. Thus, the aim of this study was to monitor bone mineral density (BMD) changes over a 16-year period of supervised exercise. Our hypothesis was that BMD differences at lumbar spine (LS) and femoral neck (FN) between exercisers (EG) and nontraining controls (CG) increased throughout the intervention with significant differences for each of the four 4-year observation periods. Sixty-seven (EG, n = 39 versus CG, n = 28) initially early-postmenopausal osteopenic women of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS) with complete BMD data sets for baseline (1998) and 4-, 8-, 12-, and 16-year follow-up were included in the analysis. The exercise protocol initially focused on a high-intensity strategy that addressed bone but increasingly shifted to a more comprehensive intervention. LS-BMD differences between the EG and CG continuously increased (year 4: 2.4% (95%- Confidence Interval 1.0% to 3.8%), year 8: 3.1% (1.6% to 4.7%), year 12: 3.9% (1.9% to 5.8), year 16: 4.5% (2.5% to 6.6%). Correspondingly, rising differences for FN-BMD (0.9% (-0.2% to 2.1%) versus 1.9% (0.4% to 3.3%) versus 2.0% (0.5% to 3.8%) versus 3.0% (1.0% to 5.0%)) were observed. However, in contrast to our hypothesis, group differences within the four 4-year periods were not consistently significant (LS, p = 0.001 to 0.097; FN, p = 0.026 to 0.673); further, BMD kinetics among the groups varied between LS and FN. Of particular importance, significant differences (p ≤ 0.030) for both regions were still found in the final period. We conclude that exercise-even when adapted for subjects' decreasing bone, health, and fitness status-is consistently effective in favorably affecting BMD in (initially) early-postmenopausal osteopenic women without any leveling-off effect after 16 years of exercise.

Effects of long-term low-dose dietary creatine supplementation in older women

ObjectiveWe aimed to investigate the effects of a one-year low-dose creatine supplementation trial on bone health, lean mass, and muscle function in older postmenopausal women. MethodsA double-blind, randomized, parallel-group, placebo controlled trial was conducted between November 2011 and November 2013 in Sao Paulo, Brazil. Postmenopausal osteopenic women were randomly allocated (1:1) into creatine (n=56; 1g/d) or placebo group (n=53; dextrose at same dose). At baseline and after one year of intervention, we assessed parameters of bone health, body composition, and muscle function. Blood parameters were also assessed before and after the intervention and adverse events were recorded throughout the trial. Possible differences in dietary intake were assessed by three 24-h dietary recalls. ResultsBone mineral density at lumbar spine, femoral neck, total femur, and whole body did not differ within- or between-groups. No significant changes in body weight, BMI, absolute and relative body fat, and body lean mass were observed. Muscle function, as assessed by timed-up-and-go and timed-stands tests, were not significantly changed within- or between-groups. Safety laboratory parameters remained unaltered. ConclusionA one-year low-dose creatine supplementation (1g/d) was free of adverse effects, but did not affect bone health parameters, lean mass, or muscle function in older women. Further studies with longer follow-up periods and higher doses of creatine supplementation are warranted. (Registered at clinicaltrials.gov as NCT01472393).

Fracture Discrimination by Trabecular Bone Score in Japanese Elderly Osteopenic Women

Fracture Discrimination by Trabecular Bone Score in Japanese Elderly Osteopenic Women

Using early biomarker data to predict long-term bone mineral density: application of semi-mechanistic bone cycle model on denosumab data.

Osteoporosis is a chronic skeletal disease characterized by low bone strength resulting in increased fracture risk. New treatments for osteoporosis are still an unmet medical need because current available treatments have various limitations. Bone mineral density (BMD) is an important endpoint for evaluating new osteoporosis treatments; however, the BMD response is often slower and less profound than that of bone turnover markers (BTMs). If the relationship between BTMs and BMD can be quantified, the BMD response can be predicted by the changes in BTM after a single dose; therefore, a decision based on BMD changes can be informed early. We have applied a bone cycle model to a phase 2 denosumab dose-ranging study in osteopenic women to quantitatively link serum denosumab pharmacokinetics, BTMs, and lumbar spine (LS) BMD. The data from two phase 3 denosumab studies in patients with low bone mass, FREEDOM and DEFEND, were used for external validation. Both internal and external visual predictive checks demonstrated that the model was capable of predicting LS BMD at the denosumab regimen of 60mg every 6months. It has been demonstrated that the model, in combination with the changes in BTMs observed from a single-dose study in men, is capable of predicting long-term BMD outcomes (e.g., LS BMD response in men after 1year of treatment) in different populations. We propose that this model can be used to inform drug development decisions for osteoporosis treatment early via evaluating LS BMD response when BTM data become available in early trials.

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.

Effects of low dose dried plum (50 g) on bone mineral density and bone biomarkers in older postmenopausal women.

Our previous findings in osteopenic postmenopausal women indicated that daily consumption of 100 g dried plum for one year is highly effective in increasing bone mineral density (BMD), as well as improving indices of bone turnover. The objective of our current study was to examine whether 50 g dried plum would be as effective as 100 g dried plum in reversing bone loss in osteopenic older postmenopausal women. Forty Eight osteopenic women (65‐79 years old) were randomly assigned into one of three treatment groups: 1) 50 g dried plum; 2) 100 g dried plum; and 3) control (0 g dried plum) with forty two subjects completing the study. All groups received 500 mg calcium and 400 IU vitamin D as a daily supplement. Blood samples were collected at baseline, three and six months to assess biomarkers of bone turnover. Physical activity recall and three‐day food records were obtained at baseline, three and six months to examine physical activity and dietary confounders as potential covariates. Both doses of dried plum significantly increased total body BMD. Tartrate resistant acid phosphatase‐5b (TRAP‐5b, a marker of bone resorption) decreased at three months and six months in both dried plum groups. These results confirm the ability of dried plum in improving BMD in older postmenopausal women and suggest that lower doses of dried plum (i.e. 50 g) may be as effective as 100 g dried plum in reversing bone loss in older, osteopenic postmenopausal women. Hence, our findings suggest that the consumption of a reasonable amount of dried plum is beneficial for older, osteopenic women.

The Effects Of A Calcium‐Collagen Chelate Dietary Supplement on Molecules Regulating Osteoclastogenesis In Osteopenic Postmenopausal Women

The use of hydrolyzed collagen dietary supplements as a means to aid in the prevention of bone loss has received considerable attention. Thirty‐nine osteopenic postmenopausal women were randomized to receive either a chelated supplement of calcium (500 mg) and enzymatically hydrolyzed collagen (5 g) (CC), and 200 IU of vitamin D3 or the same dose of calcium and vitamin D3 alone as control for one year. We found that the loss of whole body bone mineral density in women consuming CC was significantly lower than that of the control group at 12 months in those who completed the study (CC: ‐1.33% and ‐0.33% vs. control: ‐3.75% and ‐2.17%; P = .026, P = .035). In addition, serum concentrations of tartrate‐resistant acid phosphatase, an osteoclast‐derived degradative enzyme, were significantly reduced at six months in the CC group. In order to determine whether CC reduces fracture risk and better understand the mode of action by which CC and similar dietary collagen formulations act, we will assess hip fracture risk using FRAX®, and serum concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor‐κB ligand (RANKL) using enzyme‐linked immunosorbent assays. We anticipate that at six‐ and twelve‐month time points, levels of RANKL in the CC group compared to the control will be significantly lower with OPG levels unaltered, representing decreased maturation and activation of bone‐resorbing osteoclasts. The regulation of these important molecules has been reported to occur in a similar fashion with other hydrolyzed collagen formulations in rodents, but has yet to be confirmed in humans.