Efficacy of denosumab co-administered with vitamin D and Ca by baseline vitamin D status.

INTRODUCTION: In anti-osteoporosis drug trials, vitamin D and calcium (Ca) are common supplements; however, the optimal dose of each is unclear. Using data from the randomized, double-blind, placebo-controlled DIRECT trial, we assessed whether baseline serum 25-hydroxy vitamin D (25[OH]D) level influences the efficacy of denosumab co-administered with vitamin D and Ca. MATERIALS AND METHODS: In this prespecified sub-analysis, subjects with primary osteoporosis who received denosumab or placebo, plus vitamin D (≥ 400 IU/day) and Ca (≥ 600 mg/day), were classified as 25(OH)D deficient (< 20 ng/mL), insufficient (≥ 20 to < 30 ng/mL), and sufficient (≥ 30 ng/mL). Study endpoints included absolute serum 25(OH)D level at baseline, 12 months, and 24 months; change in serum 25(OH)D and bone mineral density (BMD) status from baseline; and incidence of new vertebral fractures at 24 months. RESULTS: In 475 denosumab-treated and 481 placebo-treated subjects, proportions with deficient/insufficient/sufficient 25(OH)D at baseline were 53.1%/37.1%/9.9% and 50.9%/42.0%/7.1%, respectively. Supplementation significantly increased mean serum 25(OH)D levels; at 24 months, mean levels were > 30 ng/mL (sufficient) in both treatment groups. Increase in BMD over time was higher in the denosumab group vs. placebo group in all three vitamin D status groups. At month 24, denosumab-treated subjects with deficient/insufficient baseline 25(OH)D had a significantly lower risk of new vertebral fracture vs. placebo-treated subjects. CONCLUSION: Among DIRECT trial subjects supplemented with ≥ 400 IU/day of vitamin D and ≥ 600 mg/day of Ca, baseline 25(OH)D sufficiency may not influence the efficacy of denosumab in increasing BMD or preventing vertebral fractures.

Bone Metabolism Impairment in Heart Transplant: Results From a Prospective Cohort Study.

BACKGROUND: Data on the prevention of fractures after heart transplant (HTx) are controversial in the literature. Understanding the effects of HTx on bone may guide appropriate treatments in this high-risk population. METHODS: Seventy adult HTx patients were followed for 12 months. Clinical and laboratory parameters, bone mineral density, microarchitecture, and vertebral fractures were assessed at baseline (after intensive care unit discharge) and at 6 and 12 months. Patients received recommendations regarding calcium intake and vitamin D supplementation after HTx. RESULTS: At baseline, 27% of patients had osteoporosis, associated with the length of hospitalization before HTx (P = 0.001). Bone mineral density decreased in the first 6 months, with partial recovery later. Bone microarchitecture deteriorated, mainly in the trabecular bone in the first 6 months and cortical bone in the subsequent 6 months. At baseline, 92.9% of patients had vitamin D levels <30 ng/mL and 20.0% <10 ng/mL. Patients also had calcium at the lower limit of normal, high alkaline phosphatase, and high bone resorption biomarker. These abnormalities were suggestive of impaired bone mineralization and normalized at 6 months with correction of vitamin D deficiency. The majority of vertebral fractures were identified at baseline (23% of patients). After multivariate analyses, only a lower fat mass persisted as a risk factor for vertebral fractures (odds ratio, 1.23; 95% confidence interval, 1.04-1.47; P = 0.012). CONCLUSIONS: High frequencies of densitometric osteoporosis, vitamin D deficiency, bone markers abnormalities, and vertebral fractures were observed shortly after HTx. Calcium and vitamin D supplementation should be the first step in correcting bone mineralization impairment before specific osteoporosis treatment.

ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic patients.

BACKGROUND: Osteoporosis is a systemic bone disease which leads to a reduction in bone mass. Many studies have shown that up to 80% of bone mineral density (BMD) variations are attributed to genetic factors. Arachidonate 12-lipoxygenase enzyme, encoded by the ALOX12 gene, produces lipid peroxides as reactive oxygen species (ROS), leading to oxidative stress and the development of osteoporosis. Selenium (Se) is incorporated into selenoproteins, which may reduce the risk of osteoporosis. OBJECTIVES: We aimed to investigate the association of 2 ALOX12 single nucleotide polymorphisms (SNPs) and serum Se level with lumbar spine and femoral neck BMD among elderly individuals living in Amirkola, Iran. MATERIAL AND METHODS: The study consisted of 180 individuals aged ≥60 years (90 healthy and 90 osteoporotic patients). We examined the effect of 2 ALOX12 SNPs (rs2292350 and rs9897850), using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) on both BMD regions measured by dual energy X-ray absorptiometry (DXA). Serum Se level was measured using an atomic absorption spectrophotometer PGG990 AAS (PG Instruments Ltd., Luterworth, USA). RESULTS: The rs2292350 SNP showed a significant association with femoral neck BMD (p = 0.04). Moreover, in terms of serum Se level, a significant difference was found between the patient group (57.58 ±25.54 µg/L) and the control group (81.09 ±25.58 µg/L) (p < 0.001). In addition, individuals with higher serum Se levels also had higher BMD of the lumbar spine (r2 = 0.392; p < 0.001) and the femoral neck (r2 = 0.478; p < 0.001). CONCLUSIONS: The results suggested that genetic variation in ALOX12 might influence BMD variations in our recruited participants. As for the patients with lower serum Se levels, it was observed that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the development of osteoporosis.

Beneficial effect of traditional Chinese medicine fumigation "Bone-healing Powder" in postoperative pain and recovery of neurological function of traumatic thoracolumbar spine fractures: A case-control study.

BACKGROUND: Thoracolumbar spine (TLS) fractures are commonly associated with the young healthy population, with its risk factors including both high-energy traumas and neurological deficit. The underlying mechanisms of traditional Chinese medicine (TCM) and TLS fractures have been explored. Therefore, our prospective study was conducted in order to explore the beneficial effects of TCM fumigation "Bone-healing Powder" method in both postoperative pain as well as the recovery of the patient's neurological function following healing from their traumatic TLS fractures. METHODS: Patients dealing with traumatic TLS fractures were randomly assigned into both the control and the intervention groups based on whether or not they received prior TCM fumigation in addition to any and all conventional therapy. Imaging indexes, including height of the injured vertebra (%), Cobb angle (°), horizontal displacement (%), compression area (%), sagittal diameter (%), and degree of both the swelling and pain regarding the fractures were observed and recorded both before and after the treatment for proper progression documentation. The neurological function was evaluated according to American Spinal Injury Association (ASIA) classification in order to investigate whether TCM fumigation "Bone-healing Powder" could affect the recovery of the patient's neurological function. RESULTS: Following the treatment as well as 1 year after its completion, patients who received TCM fumigation presented a higher height of their previously injured vertebra (%) and sagittal diameter (%), while a lower Cobb angle (°), horizontal displacement (%), and compression area (%) than those who were part of the conventional therapy group. A week posttreatment, patients that received TCM fumigation also showed no signs of swelling or mild pain. One year following the treatment, patients receiving TCM fumigation demonstrated an improved neurological function. CONCLUSION: These findings help to indicate that TCM fumigation "Bone-healing Powder" reduces the degrees of postoperative pain and swelling, and effectively improves recovery of the neurological function of those patients with traumatic TLS fractures, proving its worth as a clinical method in treatment.

High Prevalence of Radiological Vertebral Fractures in Women on Thyroid-Stimulating Hormone-Suppressive Therapy for Thyroid Carcinoma.

Context: Bone loss and nonvertebral fractures have been reported in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid-stimulating hormone (TSH) suppressive therapy. Radiological vertebral fractures (VFs) are an early and clinically crucial marker of bone fragility. Objective and Design: A cross-sectional study to evaluate the prevalence and determinants of radiological VFs in women receiving l-thyroxine (L-T4) therapy for DTC. Patients and Interventions: A total of 179 consecutive women (median age, 59 years; n = 178 postmenopausal) who had undergone thyroidectomy for DTC and were currently receiving L-T4 were evaluated for radiological VFs and bone mineral density (BMD). There were three TSH target levels [<0.5 mU/L, group 1 (n = 83); 0.5 to 1.0 mU/L, group 2 (n = 50); >1.0 mU/L, group 3 (n = 46)]. Results: VFs were found in 51 patients (28.5%), with significantly (P < 0.001) higher prevalence in group 1 (44.6%) as compared with group 2 (24.0%) and group 3 (4.3%). VF prevalence was not significantly different among patients in group 1 with normal BMD, osteopenia, or osteoporosis, whereas in groups 2 and 3, VFs were more frequent in patients with osteoporosis than in those with either osteopenia or normal BMD. In the whole population, VFs were significantly and independently associated with TSH level <1.0 mU/L; densitometric diagnosis of osteoporosis at lumbar spine, femoral neck, or total hip; age of patients; and duration of L-T4 therapy. Conclusion: The prevalence of VFs was high in women with DTC who were undergoing long-term, suppressive L-T4 therapy.

Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013-2014---supplementary presentation.

Spine fracture prevalence is similar in men and women, increasing from <5% in those <60 to 11% in those 70-79 and 18% in those ≥80 years. Prevalence was higher with age, lower bone mineral density (BMD), and in those meeting criteria for spine imaging. Most subjects with spine fractures were unaware of them.

Treating the Aging Spine.

Demographic trends make it incumbent on orthopaedic spine surgeons to recognize the special challenges involved in caring for older patients with spine pathology. Unique pathologies, such as osteoporosis and degenerative deformities, must be recognized and treated. Recent treatment options and recommendations for the medical optimization of bone health include vitamin D and calcium supplementation, diphosphonates, and teriparatide. Optimizing spinal fixation in elderly patients who have osteoporosis is critical; cement augmentation of pedicle screws is promising. In the management of geriatric odontoid fractures, nonsurgical support with a collar may be considered for low-demand patients, whereas surgical fixation is favored for high-demand patients. Management of degenerative deformity must address sagittal plane balance, which includes consideration of pelvic incidence. Various osteotomies may prove helpful in this setting.

Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials.

UNLABELLED: Little data exist on the frequency of fracture among oral glucocorticoid users. We examined the effect of oral glucocorticoids on fracture incidence using data from randomized controlled trials. Patients starting glucocorticoids had a higher probability of fracture and decline in bone mineral density compared to chronic glucocorticoid users. INTRODUCTION: Oral glucocorticoids (GCs) are the leading cause of secondary osteoporosis. However, there have been few studies that quantify the rate of fracture among GC users. We sought to provide a pooled estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated patients. METHODS: We updated a MEDLINE search published by the American College of Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies that reported fracture and bone mineral density (BMD) among oral GC users. We restricted the analysis to placebo or control arms. RCT arms were stratified by GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users (>6 months). Bayesian meta-regression was used to estimate the annual probability of vertebral fracture (primary), non-vertebral fracture and percentage change in lumbar spine and femoral neck BMD. RESULTS: The annual incidence of vertebral and non-vertebral fracture was 5.1 % (95 % CrI = 2.8-8.2) and 2.5 % (95 % CrI = 1.2--4.2) among GC initiators, and 3.2 % (95 % CrI = 1.8-5.0) and 3.0 % (95 % CrI = 0.8-5.9) among chronic GC users. Our meta-regression identified a non-significant effect of group-level variables (mean age, mean BMD, mean GC daily dose, patients with previous vertebral fractures, proportion of women and adjuvant used) on vertebral fracture rate. CONCLUSION: Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

CAPACITIVE COUPLING ELECTRIC FIELDS IN THE TREATMENT OF VERTEBRAL COMPRESSION FRACTURES.

Positive effects of Capacitive Coupling Electric Field (CCEF) stimulation are described for several orthopedic indications such as the healing of recent fractures, non-unions and spinal fusion, due to the capacity to involve the up-regulation of osteopromotive factors. In vitro studies on MC3T3-E1 bone cells showed that CCEF acts opening the plasma membrane voltage gated calcium channels, thus increasing the cytosolic calcium concentration and the phospholipase A2 (PLA2) activity. Cytosolic calcium activates the calmodulin pathway, thus resulting in an up-regulated expression of osteogenic genes, such as transforming growth factor-ß superfamily genes (TGF-ß1, -ß2 -ß3, bone morphogenetic protein-2 and -4), fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). PLA2 acts increasing the synthesis of Prostaglandin E2 (PGE2), which promotes osteogenesis by raising the cellular L-ascorbic acid uptake through the membrane carrier sodium vitamin C transporter-2 (SVCT-2). In vivo, Brighton et al. in a castration-induced osteoporosis animal model, demonstrated that CCEF was able to restore bone mass/unit volume in the rat vertebral body. To investigate the role of CCEF stimulation in vertebral bone marrow edema (VBME) its percentage was assessed in 24 patients with 25 acute vertebral compression fractures (VCFs) conservatively treated with CCEF (group A) or without CCEF (group B) using serial MR imaging follow-up at 0, 30, 60, 90 days. Pain and quality of life were assessed by visual analog scale (VAS) and Oswestry Low Back Disability Index (ODI) in the same periods. At 90 day follow-up the complete resolution of VBME was found only in group A (p=0.0001). A significant improvement of VAS (p=0.007) and ODI (p=0.002) was also observed in group A. This preliminary observational study shows that patients treated with CCEF stimulation present an improvement of clinical symptoms with faster fracture healing and a complete VBME resolution.

A survey of outcomes and management of patients post fragility fractures in China.

UNLABELLED: We found that the fragility hip and vertebral fractures caused excess mortality rates in this Chinese female population, which was unexpectedly lower than those in western countries and other Asian countries. This was the first nationwide survey relating to post-fracture outcomes conducted among Chinese population in Mainland China. INTRODUCTION: This study aimed to investigate the mortality, self-care ability, diagnosis, and medication treatment of osteoporosis following fragility hip and vertebral fractures through a nationwide survey among female patients aged over 50 in Mainland China. METHODS: This was a multicenter, retrospective cohort study based on medical chart review and patient questionnaire. Female patients aged 50 or older admitted for low-trauma hip or vertebral fractures and discharged from Jan 1, 2008 to Dec 31, 2012 were followed. RESULTS: Total of 1151 subjects of hip fracture and 842 subjects of vertebral fracture were included. The mean age was 73.4 ± 10.0, and the median of duration from index fracture to interview was 2.6 years. The overall 1-year, 2-year, 3-year, 4-year, and 5-year cumulative mortality rates were 3.5, 7.0, 11.2, 13.1, and 16.9 %, respectively. The first year mortality rates in hip (3.8 %, 95% CI 3.3-4.4 %) and vertebral fracture (3.1 %, 95% CI 2.5-3.7 %) were significantly higher than that in the general population (1.6 %). Impaired self-care ability was observed in 33.2, 40.6, and 23.8 % of overall, hip fracture, and vertebral fracture group, respectively. The overall diagnosis rate of osteoporosis was 56.8 %, and bone mineral density (BMD) measurement had never been conducted in 42.0 % among these women. After the index fracture, 69.6 % of them received supplements and/or anti-osteoporotic medications, among which 39.6 % only received calcium with/without vitamin D supplementation. CONCLUSIONS: The osteoporotic hip and vertebral fractures caused excess mortality rates in this population of Mainland China. The current diagnosis and medical treatment following the fragility fractures is still insufficient in Mainland China.

Management of osteoporosis in rheumatoid arthritis patients.

INTRODUCTION: In rheumatoid arthritis (RA) patients, the risk of both vertebral and non-vertebral fractures is roughly doubled, which is for an important part caused by inflammation-mediated amplification of bone loss and by immobilization. New treatments have become available in the last two decades to treat both RA and osteoporosis. AREAS COVERED: Epidemiology and assessment of osteoporosis and fracture risk (including the influence of RA disease activity and bone-influencing medications such as glucocorticoids), the importance of vertebral fracture assessment in addition to bone density measurement in patients with RA, the use of disease-modifying antirheumatic drugs and their effects on generalized bone loss, and current and possible future anti-osteoporotic pharmacotherapeutic options are discussed with special focus on RA. EXPERT OPINION: Assessment of osteoporosis in RA patients should include evaluation of the effects of disease activity and bone-influencing medications such as (the dose of) glucocorticoids, above standard risk factors for fractures or osteoporosis as defined by the FRAX instrument. Disease-modifying antirheumatic drugs are now well able to control disease activity using treat to target strategies. This lowering of disease activity by antirheumatic medications such as anti-TNF-α results in hampering of generalized bone loss; however, no fracture data are currently available. When treating osteoporosis in RA patients, additional focus should be on calcium supplementation, particularly in glucocorticoid users, and also on sufficient vitamin D use. Several anti-osteoporotic medications are now on the market; oral bisphosphonates are most commonly used, but in recent years, more agents have entered the market such as the parenteral antiresorptives denosumab (twice yearly) and zoledronic acid (once yearly), and the anabolic agent parathyroid hormone analogues. New agents, such as odanacatib and monoclonal antibodies against sclerostin, are now being tested and will most likely enlarge the possibilities of osteoporosis treatment in RA patients.

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT).

SUMMARY: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. INTRODUCTION: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. METHODS: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. RESULTS: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. CONCLUSIONS: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.

The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body.

UNLABELLED: The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR-pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. METHODS: Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4° wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. RESULTS: For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD.

An in silico parametric model of vertebrae trabecular bone based on density and microstructural parameters to assess risk of fracture in osteoporosis.

Osteoporosis is a progressive bone disease characterized by deterioration in the quantity and quality of bone, leading to inferior mechanical properties and an increased risk of fracture. Current assessment of osteoporosis is typically based on bone densitometry tools such as Quantitative Computed Tomography (QCT) and Dual Energy X-ray absorptiometry (DEXA). These assessment modalities mainly rely on estimating the bone mineral density (BMD). Hence present densitometry tools describe only the deterioration of the quantity of bone associated with the disease and not the affected morphology or microstructural changes, resulting in potential incomplete assessment, many undetected patients, and unexplained fractures. In this study, an in-silico parametric model of vertebral trabecular bone incorporating both material and microstructural parameters was developed towards the accurate assessment of osteoporosis and the consequent risk of bone fracture. The model confirms that the mechanical properties such as strength and stiffness of vertebral trabecular tissue are highly influenced by material properties as well as morphology characteristics such as connectivity, which reflects the quality of connected inter-trabecular parts. The FE cellular solid model presented here provides a holistic approach that incorporates both material and microstructural elements associated with the degenerative process, and hence has the potential to provide clinical practitioners and researchers with more accurate assessment method for the degenerative changes leading to inferior mechanical properties and increased fracture risk associated with age and/or disease such as Osteoporosis.

The Auckland calcium study: 5-year post-trial follow-up.

UNLABELLED: Five years after completion of a randomised placebo-controlled trial of calcium supplements, there was no effect of calcium on total fracture incidence, a significant reduction in vertebral and forearm fractures and, in a subset, no effect on bone density. There was no increased risk of cardiovascular events after discontinuation of calcium. INTRODUCTION: The Auckland calcium study was a 5-year randomised controlled trial of 1 g/day calcium citrate in 1,471 postmenopausal women. Calcium did not reduce total, vertebral or forearm fracture incidence, increased hip fracture incidence and had beneficial effects on bone mineral density (BMD). A secondary analysis raised concerns about the cardiovascular safety of calcium. The purpose of this study was to determine whether the effects of calcium on fracture incidence, BMD and cardiovascular endpoints persisted after supplement discontinuation. METHODS: Approximately 5-years post-trial, we collected information on the 1,408 participants alive at trial completion from the national databases of hospital admissions and deaths. We contacted 1,174 women by phone, and from these we obtained information on medical events and post-trial calcium use. We undertook BMD measurements at 10 years in a selected subset of 194 women who took study medication for 5 years in the original trial, and did not take bone-active medications post-trial. RESULTS: Over the 10-year period, there was no effect on total fracture (HR 0.90, 95% CI 0.75-1.07) or hip fracture incidence (1.40, 0.89-2.21), but significant reductions in forearm (0.62, 0.43-0.89) and vertebral fractures (0.52, 0.32-0.85) in those assigned to calcium. There were no between-group differences in BMD at 10 years at any site. The adverse cardiovascular outcomes observed in the 5-year trial did not persist post-trial. CONCLUSION: Calcium supplementation for 5 years had no effect on total fracture incidence at 10 years. The positive benefits on BMD and the adverse cardiovascular effects did not persist once supplements were stopped.

Effect of intermittent PTH (1-34) on posterolateral spinal fusion with iliac crest bone graft in an ovariectomized rat model.

SUMMARY: Intermittent treatment with high-dose parathyroid hormone (PTH) enhances the quantity and quality of the fusion callus and reduces healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats. Intermittent PTH (1-34) could be an appropriate adjunctive therapy for osteoporotic patients undergoing posterolateral intertransverse process fusion. INTRODUCTION: The study was designed to test the hypothesis that intermittent administration of PTH improves spinal fusion rates in a randomized controlled, ovariectomized osteoporotic rat spinal fusion model. METHODS: Thirty-six 10-week-old Sprague-Dawley rats were ovariectomized and underwent bilateral posterolateral L4-L5 spinal fusion with autologous iliac bone graft 6 weeks later. The experimental (PTH) group (18 rats) received daily subcutaneously administered injections of PTH (1-34) at 30 µg/kg/day starting on the day of operation. The control group (18 rats) received a subcutaneously administered injection of normal saline of the same volume. Nine rats from each group were sacrificed at 4 and 6 weeks. After sacrifice, the L4-L5 vertebral segments were removed and analyzed by plain radiographs, µ-CT, histomorphometry, and serum bone metabolism marker. RESULTS: The PTH group had a significantly higher fusion rate and X-ray fusion score than the control group at 4 and 6 weeks (p < 0.05). µ-CT and histological analysis showed that the fusion bone volume and cortical thickness for the PTH group were significantly higher than those for the control group at 4 and 6 weeks (p < 0.05). Metabolic marker analysis also showed significant difference between the two groups. The serum osteocalcin was significantly higher in the PTH group at 4 and 6 weeks, and levels of N-terminal peptide of type I collagen were significantly higher at 4 weeks (p < 0.05). CONCLUSION: Intermittent treatment with high-dose PTH enhances the quantity of the fusion callus and reduces the healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats.

Exercise for patients with osteoporosis: management of vertebral compression fractures and trunk strengthening for fall prevention.

Maintenance of bone health and quality requires mechanical strain, but the mechanical force needs to be within the bone's biomechanical competence. In osteoporosis, compression of vertebral bodies can be insidious. Therefore, absence of pain does not necessarily indicate absence of vertebral microfracture and deformity. Further, patients with previous vertebral fractures are at risk for further vertebral fractures and their associated morbidity. Exercise is a part of the comprehensive management of patients with osteoporosis and has been associated with improvement of quality of life and lowered risk of future fracture. The exercise prescription needs to match the needs of the patient. If exercise is not prescribed properly, then it may have negative consequences. In general, an exercise program, therapeutic or recreational, needs to address flexibility, muscle strength, core stability, cardiovascular fitness, and gait steadiness. As with pharmacotherapy, therapeutic exercises need to be individualized on the basis of musculoskeletal status and an individual's exercise interest. In osteoporosis, axial strength and stability are of primary importance. In particular, a spinal extensor strengthening program should be performed with progressive measured resistance as tolerated. To address falls and fractures, an exercise program should also include balance and lower extremity strength training. Proper dosing of oral cholecalciferol and calcium supplements can enhance the effect of strengthening exercises. Finally, a coordinated approach, such as the Spinal Proprioception Extension Exercise Dynamic (SPEED) program, can improve back extensor strength, the level of physical activity, and locomotion, and reduce back pain and fear and risk of falls.

A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study.

BACKGROUND: Eldecalcitol is an analog of 1,25-dihydroxyvitamin D(3) that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. METHODS AND RESULTS: This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 µg eldecalcitol versus 1.0 µg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50 nmol/L) were supplemented with 400 IU/day vitamin D(3). Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. CONCLUSIONS: Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.

Vulnerability of healthy vertebrae in patients with and without previous vertebral fracture.

Vertebral deformities are associated with a marked increase in morbidity, mortality, and burden in terms of sanitary expenditures. Patients with vertebral fractures have a negative impact in their health, less quality of life, and loss of functional capacity and independence. The purpose of this study was to explore the vulnerability of healthy vertebrae in patients who have sustained already a compression fracture and in patients who do not have prevalent fractures in the thoracic spine; and to explore the association of the deformity in healthy vertebrae with different variables, such as bone mineral density (BMD), body mass index, age, loss of height, presence of clinical kyphosis, history of other osteoporotic fractures, and falls occurring during the last year. Clinical data and complementary studies from 175 postmenopausal outpatients were analyzed. These women (age: 69.7±11.1 years) had not received any treatment for osteoporosis. Anteroposterior and lateral radiographs of the thoracic spine and bone densitometry of the hip were obtained; morphometry was performed in 1575 thoracic vertebrae from T4 to T12. The angle of wedging of each vertebral body was calculated using a trigonometric formula. Then, the sum of wedge angles of vertebral bodies (SWA) was determined, and Cobb angle was measured. In patients with vertebral fractures, after excluding the angles of fractured vertebral bodies, the mean wedge angle of the remaining vertebrae (MWAhealthy) was calculated. The same procedure was followed in patients without vertebral fractures. MWAhealthy was considered as an indicator of the structural vulnerability of non-fractured vertebrae. Patients with prevalent fractures had lower BMD, wider Cobb angle, and higher sum of wedge angles than patients without vertebral fractures. The proportion of patients with accentuation of clinical kyphosis was higher in the group with prevalent vertebral fractures. A highly significant difference was found in the MWAhealthy, which was higher in patients with prevalent fractures (4.1±1.3° vs. 3.0±1.1°; p<0.001). Patients showing vertebral fractures had 7.1±4.2 cm height loss in average, significantly superior than that found among non-fractured women (3.6±3.2 cm; p<0.01). In multivariate analysis, the increase of MWAhealthy was associated with advancing age (p<0.02), lower femoral neck BMD (p<0.005), presence of clinical kyphosis (p<0.01) and vertebral fractures (p<0.02). This study presents evidence that a series of factors independently influence the increase in wedging deformity of vertebral bodies that are not fractured yet. These factors could contribute to an increased vulnerability of the vertebrae, making them more susceptible to fracture.

Capacitively coupled electric field for pain relief in patients with vertebral fractures and chronic pain.

UNLABELLED: Fragility vertebral fractures often are associated with chronic back pain controlled by analgesic compounds. Capacitive coupling electrical stimulation is a type of electrical stimulation technology approved by the US FDA to noninvasively enhance fracture repair and spinal fusion. These uses suggest it would be a possible treatment for patients with back pain attributable to vertebral fractures. We therefore randomized 51 postmenopausal women with multiple fractures and chronic pain to the use of one of two indistinguishable devices delivering either the standard capacitive coupling electrical stimulation by Osteospine (active group) or low intensity pulse (control group). Twenty patients of the active group and 21 of the control group (80%) completed the study for a total duration of 3 months. The mean visual analog scale values for pain and the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) scores improved in both groups. We observed a relationship between hours of treatments and reductions in pain intensity only in the active group. Capacitive coupling electrical stimulation was not more effective than control treatment when comparing mean visual analog scale pain and QALEFFO scores in the two groups and when adjusting for the hours of treatment. However, the proportion of patients able to discontinue NSAIDs owing to elimination or reduction of pain was greater in the active group than in the control group. We interpret these findings as suggesting capacitive coupling electrical stimulation controls pain in some patients and reduces the use of NSAIDs. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.