Bone Mineral Density Response Research Articles

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis

BackgroundTeriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment.MethodsIn this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months.ResultsTwelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment.ConclusionOur results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Bone loss and new vertebral fractures during treatment with romosozumab: a case-report

PurposeThis study aimed to illustrate the possibility of an unfavorable response to treatment with the anabolic agent romosozumab for patients with severe osteoporosis and to discuss explanations for treatment failure.MethodsDual-energy x-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and X-rays of the thoracolumbar spine was used to assess bone mineral density (BMD) and the presence of vertebral fractures before and after treatment with romosozumab.ResultsOur patient developed a decrease in the BMD of the hip, two incident new vertebral fractures, and worsening of one prevalent vertebral fracture during 1 year treatment with romosozumab. We have not detected non-adherence, there was no pretreatment with anti-resorptives, and we observed no signs of secondary osteoporosis and/or comorbidities.ConclusionAs the number of patients treated with romosozumab is rising, it becomes more likely that more patients will be found with new fractures and/or an unfavorable BMD response. Probably, the unfavorable response is a (bad) chance finding, but we think it is crucial for clinicians and patients to exclude nonadherence, new comorbidities and pretreatment with anti-resorptives as explanation in these patients.

Effects of Vitamin D Supplementation in Elite Athletes: A Systematic Review.

Deficiency in vitamin D has been shown to increase the risk of injury. To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health. Systematic review; Level of evidence, 1. A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations. Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 (P < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation (P = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels (P < .05). Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.

Modulation of Bone Mineral Density and Its Response to Menopausal Hormone Therapy according to the Apolipoprotein E Genotype in Postmenopausal Korean Women.

Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women. This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically. Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck. Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT.

Coronary artery calcification is associated with smaller increases in femoral neck bone mineral density with anti-resorptive therapy

Abstract Introduction Patients with osteoporosis are at high cardiovascular risk, partly due to vascular calcification, such as in the coronary vessels. It is uncertain if the presence of coronary artery calcification (CAC) effects bone mineral density (BMD) response to anti-resorptive treatment – first line therapy for osteoporosis. We therefore assessed changes in BMD following initiation of anti-resorptive treatment for osteoporosis in patients with and without evidence of CAC. Methods Individuals dispensed at least one prescription for an anti-resorptive medication (bisphosphonates or denosumab) at Monash Health between 2009-2022 were identified. Unique record numbers for these individuals were then cross-matched against the cardiac CT imaging service at Monash Heart (HREC#73603). CAC was detected using a 320-slice CT coronary angiogram (CTCA). We included only those patients having a baseline BMD measurement within two years of CTCA. The annualised percentage change in femoral neck BMD was calculated and adjusted for age, sex, height, weight, and number of years on anti-resorptive treatment. Results 106 individuals were identified of which 85 (women=70 [85%], median age=73 years [interquartile range 64-79 years]) had a follow-up BMD measurement including 19 with, and 66 without, evidence of CAC. Those with CAC were older (76 years versus 64 years, p&amp;lt;0.001). There were 70 bisphosphonate users and 15 denosumab users. Individuals with evidence of CAC experienced, on average, a 1.2% lower increase [(0.345% (0.343 to 0.348) versus -0.881% (-0.883 to -0.879), mean difference -1.226% (-1.493 to -0.959; p&amp;lt;0.05)] in annualised femoral neck BMD with anti-resorptive therapy after adjusting for important clinical risk factors. Interpretation These preliminary data suggests that CTCA-determined CAC may negatively impact femoral neck BMD increases with anti-resorptive therapy. This is perhaps consistent with existing and evolving hypotheses of dysregulatory processes driving ectopic calcium deposition, which we surmise would partially counter the effects of anti-resorptive therapy and potentially manifest as CAC. Thus, of particular interest will be the comparison of cardiovascular outcomes of patients with known CAC with and without anti-resorptive therapy, with the hypothesis that anti-resorptive therapy may potentially have cardioprotective effects in context of CAC. Analysis of the full cohort is underway.Table 1

Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target

We examined the effects of ∼30days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3β content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3β was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3. We then tested the effects of inhibiting GSK3 before this fiber type shift, and we demonstrate that muscle-specific Gsk3 knockdown increased muscle mass, preserved muscle strength, and promoted the oxidative fiber type with Earth-based hindlimb unloading. In bone, GSK3 activation was enhanced after spaceflight; and strikingly, muscle-specific Gsk3 deletion increased bone mineral density in response to hindlimb unloading. Thus, future studies should test the effects of GSK3 inhibition during spaceflight.

Bone Mineral Density Response to Long-Term Bisphosphonate Treatment and Discontinuation in a Real-World Clinical Service

ObjectiveBisphosphonate treatment does not increase bone mineral density (BMD) in all subjects particularly at the femoral neck (FN). Our aim was to evaluate the relationship between response to oral bisphosphonate (oBP) at the FN and change in BMD following discontinuation. MethodsData were collected retrospectively from postmenopausal women on oBP for ≥3 years, attending a real-world metabolic clinic at initiation of oBP, discontinuation, and 1 to 2 years post discontinuation. Improvement in BMD ≥4% in the FN and ≥5% for the lumbar spine (LS) were deemed clinically meaningful and used as least significant change (LSC) values. We divided subjects based on FN BMD response and compared outcomes between responders and non-responders after oBP discontinuation. ResultsOf the 213 subjects, 32.1% showed an increase ≥LSC at the FN compared to 57.1% at the LS on treatment (P < .0001). FN responders had lower BMD levels at pretreatment baseline than non-responders both at the FN (0.58 vs 0.62 g/cm2; P = .003) and LS (0.76 vs 0.79 g/cm2; P = .044). Off-treatment, more subjects lost BMD ≥LSC at FN in the responder group than in the non-responder group (37.5% vs 14.2%; P < .001). BMD remained above pre-treatment levels in responders after a median follow-up of 1.52 years. ConclusionBMD response at FN is suboptimal in patients on oBP and is much less common than LS response. FN responders tend to lose the accumulated bone quickly off-treatment, though BMD remains above pretreatment levels. These observations suggest that new approaches may be needed to optimize osteoporosis management in real-world patients.

Abstract #1377932: An Inherited Metabolic Disorder That Masquerades as Osteoporosis

Hypophosphatasia is a rare genetic disorder caused by loss-of-function mutations in the ALPL gene, which encodes tissue non-specific alkaline phosphatase. The enzyme defect results in the accumulation of substrates like inorganic pyrophosphate, thereby inhibiting mineralization of bones and teeth. Clinical features include premature loss of deciduous teeth, bowed legs, lower extremity stress fractures, bone pain and impaired mobility. Serum alkaline phosphatase (ALP) is a marker of bone turnover. Low ALP, high serum vitamin B6 and high urine phosphoethanolamine are diagnostic hallmarks of hypophosphatasia. A 54-year-old lady was referred to the endocrinology clinic for severe osteoporosis, characterized by an olecranon fracture and low bone mineral density (T score -3.0 at the left femoral neck). Bone disease risk factors included premature menopause at age 38 years and maternal history of hip fracture. There was no personal or family history of recurrent fractures, impaired mobility, or unexplained tooth loss. Despite treatment with ibandronate, zoledronic acid and teriparatide, her bone mineral density declined over the course of a decade. Physical examination revealed low BMI (18.07 kg/m2), normal gait and intact muscle strength. Lab testing disclosed low serum alkaline phosphatase (ALP) 18 units/L [reference 45 to 117 units/L], high serum vitamin B6 131.8 nmol/L [reference 20.0 to 125.0 nmol/L] and high urine phosphoethanolamine 104 nmol/mg Cr [reference < 48]. ALP results prior to bisphosphonate exposure were unavailable. Vitamin D status, thyroid function, parathyroid hormone, corrected serum calcium, ceruloplasmin and zinc levels were normal. Exome sequencing identified a pathogenic heterozygous nonsense ALPL gene mutation, c.1282C >T (p.Arg428X). She was counselled to avoid bisphosphonate therapy indefinitely. ALP measurement was advised for her blood relatives since hypophosphatasia is an autosomal recessive or dominant disorder. With asfotase alfa, the only FDA-approved therapy for juvenile-onset hypophosphatasia, there have been no further fractures to date, and her mobility remains unimpaired. Hypophosphatasia can be mistaken for osteoporosis since both conditions present with low bone mineral density on DEXA scan. Furthermore, bisphosphonate therapy and hypophosphatasia are mutually exclusive entities that can present with low ALP. Thus, bisphosphonate exposure may pose a diagnostic quandary when distinguishing between osteoporosis and hypophosphatasia. This case highlights the importance of assessing ALP when evaluating osteoporosis with atypical features such as age of onset under fifty years, remarkably low bone mineral density, fracture(s), and inadequate response to anti-osteoporosis agents. Moreover, if ALP is low, some index of suspicion for hypophosphatasia ought to be maintained, even if dental or lower extremity bone symptoms are absent. Genetic testing is confirmatory. Bisphosphonate therapy and parathyroid hormone analogs are not established treatment modalities for hypophosphatasia. Instead, enzyme replacement with asfotase alfa is recommended.

A retrospective analysis of nonresponse to denosumab after hip fractures

Denosumab is an effective antiresorptive drug commonly prescribed for the treatment of osteoporosis. However, some patients do not respond well to denosumab treatment. The aim of this study was to evaluate the factors underlying treatment nonresponses to denosumab in elderly patients following hip fracture. This retrospective study included 130 patients treated with denosumab after osteoporotic hip fracture between March 2017 and March 2020. The patients were categorized as denosumab nonresponders if they had a T-score <-3 that persisted between dual-energy X-ray absorptiometry scans, a >3% decrease in bone mineral density (BMD), or an incident fracture on denosumab therapy. We examined the baseline characteristics associated with blunted BMD responses and compared the groups following denosumab treatment for 12 months. Of 130 patients with baseline data, 105 patients (80.8%) were considered responders. No difference in baseline vitamin D, calcium, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and nonresponders. A longer interval between denosumab injections was associated with suboptimal BMD response at both spine and total hip (p<0.001 and p=0.04, respectively). The overall L-BMD and H-BMD were significantly increased compared with pretreatment levels after denosumab treatment (5.7% and 2.5%, respectively). This study revealed that nonresponse was not strongly associated with certain baseline variables and it appears that the reponders and nonresponders were reasonably comparable in this study population. The results of our study highlight the importance of timely denosumab administration when using this drug for osteoporosis management. Physicians should keep these results in mind in clinical practice so that they can improve utilization of 6-month denosumab.

Response of bone mineral density and balance performance in post-burn patients with selected Qigong training: A single-blind randomized controlled trial

BackgroundDecreased bone mineral density (BMD) is a common condition after a burn with significant complications that would be a global health problem. Also, balance can further worsen due to burning complications. Therefore, this study aims to analyze the additive effects of selected Qigong training exercises for 2 months to the standard physiotherapy regimen on bone mineral density and balance control post-thermal burn injuries. Methods110 participants (75 males and 35 females), aged 25–50, with deep second and third-degree thermal burns affecting the trunk and lower extremities, and a total body surface area (TBSA) of 30–45%, allocated randomly into two equal groups of 55. Group A has Qigong training along with its standard physiotherapy regimen, and the control group (Group B) has only a standard physiotherapy regimen. For eight weeks, the interventions were used four times a week. The bone mineral density (BMD), T-score of the lumbar spine, the overall stability index (OSI), and the dynamic limits of stability (DLOS) were assessed pre-intervention and after eight weeks of intervention. ResultsA two-way mixed MANOVA showed that there was a significant increase in BMD, T-score, and DLOS and a significant decrease in OSI in a favor of the Qigong training group after eight weeks of treatment compared with that of the control group. Both groups showed a significant improvement in BMD, T- score, DLOS, and OSI post-treatment compared with that at the baseline. There were statistical significances in the favor of the Qigong training group after eight weeks of treatment (P < 0.001). ConclusionIn patients with repaired second and third-degree thermal burns of the trunk and lower legs, Qigong training activities combined with a standard physiotherapy regimen for 2 months were more helpful in increasing bone mineral density and improving balance control than the standard physiotherapy regimen alone.

Genome-wide association study identifies genetic variants which predict the response of bone mineral density to teriparatide therapy

ObjectivesTeriparatide (TPTD) is an effective treatment for osteoporosis but the individual response to therapy is variable for reasons that are unclear. This study aimed to determine whether the response to...

Bone mineral density response to antiosteoporotic drugs in older depressed adults.

This study aimed to evaluate the effects of depression and antidepressants on bone mineral density (BMD) and response to antiosteoporotic agents in older adults. A total of 198 participants with osteoporosis, aged 65 and over, were included in this retrospective study. BMD was measured by dual-energy x-ray absorptiometry scanning at baseline and month 24. Eighty-three of the 198 patients had a diagnosis of depression, and all were serotonergic antidepressant users. Baseline BMD was similar in depressed and non-depressed patients. Lumbar spine BMD change was significantly lower in depressed patients than non-depressed patients (2.89% and 4.85%, respectively, p < 0.001). In addition, of those receiving denosumab treatment, depressed ones had lower lumbar spine BMD changes. Depression and/or antidepressant use was an independent variable for non-response to osteoporosis treatment in both the femoral neck (p = 0.008, OR = 2.61) and lumbar spine (p = 0.015, OR = 6.87), while alendronate and zoledronic acid were independent variables for non-response in the femoral neck and total femur compared to denosumab. Our study has shown that the presence of depression and/or serotonergic antidepressant use was associated with non-response to osteoporosis treatment in older adults. The results of our study may guide physicians to make treatment decisions in older individuals with depression.

Polymorphisms in Genes Encoding VDR, CALCR and Antioxidant Enzymes as Predictors of Bone Tissue Condition in Young, Healthy Men.

The aim of the study was to assess significant predictors of bone mineral content (BMC) and bone mineral density (BMD) in a group of young, healthy men at the time of reaching peak bone mass. Regression analyses showed that age, BMI and practicing combat sports and team sports at a competitive level (trained vs. untrained group; TR vs. CON, respectively) were positive predictors of BMD/BMC values at various skeletal sites. In addition, genetic polymorphisms were among the predictors. In the whole population studied, at almost all measured skeletal sites, the SOD2 AG genotype proved to be a negative predictor of BMC, while the VDR FokI GG genotype was a negative predictor of BMD. In contrast, the CALCR AG genotype was a positive predictor of arm BMD. ANOVA analyses showed that, regarding SOD2 polymorphism, the TR group was responsible for the significant intergenotypic differences in BMC that were observed in the whole study population (i.e., lower BMC values of leg, trunk and whole body were observed in AG TR compared to AA TR). On the other hand, higher BMC at L1-L4 was observed in the SOD2 GG genotype of the TR group compared to in the same genotype of the CON group. For the FokI polymorphism, BMD at L1-L4 was higher in AG TR than in AG CON. In turn, the CALCR AA genotype in the TR group had higher arm BMD compared to the same genotype in the CON group. In conclusion, SOD2, VDR FokI and CALCR polymorphisms seem to affect the association of BMC/BMD values with training status. In general, at least within the VDR FokI and CALCR polymorphisms, less favorable genotypes in terms of BMD (i.e., FokI AG and CALCR AA) appear to be associated with a greater BMD response to sports training. This suggests that, in healthy men during the period of bone mass formation, sports training (combat and team sports) may attenuate the negative impact of genetic factors on bone tissue condition, possibly reducing the risk of osteoporosis in later age.

RF30 | PSAT138 Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient with Hypophosphatasia

Abstract Background Hypophosphatasia (HPP) is a rare inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with concomitant HPP are limited due to concerns for a greater likelihood of atypical femoral fractures (AFF) with anti-resorptive agents such as bisphosphonates and denosumab. We present a patient with HPP and OP who was treated with the anti-sclerostin antibody romosozumab-aqqg (Romo). Clinical Case An 81-year-old female was referred for management of OP. Fracture history included a hip fracture around age 40, and bilateral metatarsal fractures around age 65. Her initial DXA scan at age 57 showed osteoporosis at the lumbar spine (LS, T-score: -2.8) and femoral neck (FN, T-score -3.2). Sequential osteoporosis treatment over the subsequent 20 years included several years of oral bisphosphonates, hormone replacement therapy, teriparatide for one year followed by two years of alendronate, and one denosumab injection. Despite almost 20 years of pharmacologic osteoporosis treatment, her bone mineral density (BMD) worsened. HPP was suspected on the basis of low serum alkaline phosphatase (AP) levels ranging from 25-37 U/L (ref: 35-104 U/L). The diagnosis was substantiated by an elevated plasma vitamin B6 level of 305 mcg/L (ref: 5-50 mcg/L) and confirmed by genetic testing showing a diagnostic missense mutation c.571G&amp;gt;A in exon 6 in the ALPL gene. After diagnosing HPP, her osteoporosis was treated with an additional year of teriparatide followed by raloxifene, which she tolerated poorly. Following two years of expectant management, during which time her BMD worsened despite calcium and vitamin D supplementation to T-scores of –4.4 at the LS, she was started on Romo. After 11 monthly injections, a follow up DXA scan showed improvements of 21%, and 10% at the LS and total hip, respectively. These changes were substantially greater than what she experienced with her first year of teriparatide therapy (+4% and +8%, respectively). Blood AP remained low on Romo (37 IU/L and 29 IU/L at 9 and 12 months post-Romo initiation). She tolerated Romo and well and experienced no fractures during treatment. Discussion Management of osteoporosis in patients with HPP is challenging, as bisphosphonates and denosumab are generally avoided due to concern for an increased risk of AFF. Case reports of patients with HPP have suggested good BMD response to teriparatide. To our knowledge, this is the first report of a patient with HPP and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum AP, but improved BMD significantly more than in response to teriparatide. In conclusion, Romo is a potential treatment option for OP in patients with HPP for whom limited alternatives exist. Optimal osteoporosis treatment following a 1-year course of Romo remains to be determined. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:05 p.m. - 1:11 p.m.

Comparison of antiresorptive agents in the treatment of osteoporosis in older adults

Purpose: There are few studies comparing the effectiveness of anti-osteoporotic drugs among elderly population. In this study, we aimed to compare the effectiveness of alendronate, zoledronic acid, and denosumab in older adults. &#x0D; Materials and Methods: A total of 350 older adults with osteoporosis, aged 65 and over were included in this retrospective study. The number of patients receiving alendronate, zoledronic acid, and denosumab was 111, 121, and 118, respectively. Bone mineral density (BMD) was measured at baseline and 24th month by performing dual-energy x-ray absorptiometry (DXA) scans.&#x0D; Results: The age, comorbidities, and laboratory analysis results of the patients were similar. While there was no statistically significant difference in BMD response at the femoral neck between the treatment groups (Baseline BMDs for alendronate, zoledronic acid, and denosumab were 0.61, 0.59, and 0.58, respectively, while 24th month BMDs were 0.62, 0.60, and 0.59, respectively), alendronate and zoledronic acid improved lumbar spine BMD more than denosumab (Baseline BMDs for alendronate, zoledronic acid, and denosumab were 0.74, 0.74, and 0.71, respectively, while 24th month BMDs were 0.77, 0.78, and 0.73).&#x0D; Conclusion: This study has shown that, like parenteral antiresorptive agents, alendronate can elicit a desirable BMD response in older osteoporotic adults. The results of our study may guide osteoporosis treatment in older individuals.

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women.

The aim of this study was to explore the allelic association between genetic polymorphisms of the NF-κB pathway and the variance of clinical effects of zoledronic in postmenopausal Chinese women with osteoporosis. In the study, 110 Chinese postmenopausal women with osteoporosis were recruited. Every patient received zoledronic once a year. BMD was measured at baseline and after one year of treatment. The 13 tagger SNPs of five genes in the NF-κB pathway were genotyped. In the study, 101 subjects completed the one-year follow-up. The ITCTG and DTCTG haplotypes, which are constituted of rs28362491, rs3774937, rs230521, rs230510 and rs4648068 of the NF-κB1 gene, were associated with improvement in BMD at L1-4 and femoral neck (p < 0.001, p = 0.008, respectively). The CGC haplotype, which is constituted of rs7119750, rs2306365 and rs11820062 of the RELA gene, was associated with improvement in BMD at total hip (p < 0.001). After Bonferroni correction, haplotypes ITCTG and CGC still showed significant association with the % change of BMD at L1-4 and total hip. Therefore, NF-κB1 and RELA gene were significantly associated with bone response to the treatment of zoledronic in postmenopausal Chinese women with osteoporosis.

Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial

Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen+Cal, n=40, mean±SEM age: 21.3±0.5 y; weight: 55.0±1.0kg; BMI: 20.4±0.3kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n=36; mean±SEM age: 20.7±0.5 y; weight: 59.1±1.3kg; BMI: 21.3±0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. Oligo/Amen+Cal improved energy status [increased body mass (2.6±0.4kg), BMI (0.9±0.2 kg/m2), fat mass (2.0±0.3kg), body fat percentage (2.7%±0.4%), and insulin-like growth factor 1 (37.4±14.6ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P<0.05). Total body and spine aBMD remained unchanged (P>0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.0002g/cm2 ; time main effect P=0.043) and month 12 (-0.011g/cm2; 95% CI: -0.021, -0.001g/cm2; time main effect P=0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.002g/cm2; time main effect P=0.004). Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873.

Evaluation of early bilateral ovariectomy in mice as a model of left heart disease.

Postmenopausal women tend to have worse cardiovascular outcomes in a manner that is associated with osteoporosis severity. In this study, we performed the first evaluation of the left ventricle and aortic valve phenotype of ovariectomized mice aged on Western diet to 1 yr. Disease was monitored in vivo using echocardiography and dual X-ray absorptiometry imaging and ex vivo using quantitative histological and immunostaining analysis. Mice had decreased bone mineral density in response to ovariectomy and increased fat mass in response to Western diet. Ovariectomized mice had a significantly increased left ventricle mass compared with control animals, absent of fibrosis. There was a slight increase in aortic valve peak velocity but no change in mean pressure gradient across the valve in the ovariectomy group. There was no evidence of leaflet hypertrophy, fibrosis, or calcification. This model of ovariectomy may present a novel method of studying left ventricle hypertrophy in female populations but does not have a phenotype for the study of aortic stenosis. This is particularly useful as it does not require genetic manipulation or drug treatment and more faithfully mimics aging, high-cholesterol diet, and postmenopausal osteoporosis that many female patients experience potentially resulting in a more translatable disease model.NEW & NOTEWORTHY This article uses in vivo and ex vivo analysis to track the development of osteoporosis and left heart cardiovascular disease in an aged, high-cholesterol diet, mouse ovariectomy model. Mice develop early left ventricle hypertrophy without concurrent fibrosis or aortic valve stenosis. These findings allow for a new model of the study of left ventricle hypertrophy in postmenopausal osteoporosis that more closely mimics the natural progression of disease in female patients.

The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury.

Spinal cord injury (SCI) produces paralysis and a unique form of neurogenic disuse osteoporosis that dramatically increases fracture risk at the distal femur and proximal tibia. This bone loss is driven by heightened bone resorption and near-absent bone formation during the acute post-SCI recovery phase and by a more traditional high-turnover osteopenia that emerges more chronically, which is likely influenced by the continual neural impairment and musculoskeletal unloading. These observations have stimulated interest in specialized exercise or activity-based physical therapy (ABPT) modalities (e.g., neuromuscular or functional electrical stimulation cycling, rowing, or resistance training, as well as other standing, walking, or partial weight-bearing interventions) that reload the paralyzed limbs and promote muscle recovery and use-dependent neuroplasticity. However, only sparse and relatively inconsistent evidence supports the ability of these physical rehabilitation regimens to influence bone metabolism or to increase bone mineral density (BMD) at the most fracture-prone sites in persons with severe SCI. This review discusses the pathophysiology and cellular/molecular mechanisms that influence bone loss after SCI, describes studies evaluating bone turnover and BMD responses to ABPTs during acute versus chronic SCI, identifies factors that may impact the bone responses to ABPT, and provides recommendations to optimize ABPTs for bone recovery.

Association between P1NP and bone strength in postmenopausal women treated with teriparatide

ObjectiveTo evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. Materials and MethodsThis prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. ResultsWith teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. ConclusionP1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.