Significant Increase In BMD Research Articles

THU438 A Case Of Pregnancy Associated Osteoporosis

Abstract Disclosure: S. Maradana: None. F. Iqbal: None. M. Safran: None. Background: Pregnancy associated osteoporosis (PAO) is a rare form of osteoporosis that is seen in late pregnancy and early post-partum period. Hip and vertebral body are most involved in PAO. Common clinical manifestation is back pain, and many patients suffer from vertebral fractures and kyphosis causing great physiologic burden and negative impact on quality of life. We report a case of PAO with good response to teriparatide. Clinical case: A 27-year-old female with no significant past medical history presented with severe acute back pain two months after delivery of her second child, whilst still breast feeding. Imaging studies demonstrated acute compression fractures of T12, L1, L2 and L3 vertebrae. She had regular monthly menstrual cycles prior to pregnancy with no previous history of fractures. Her pre pregnancy weight was 135 lbs and she had been physically active, while caring for her older son. Family history is notable for osteoporosis in multiple paternal aunts and maternal grandmother with no family history of fractures. There were no other identifiable risk factors. Evaluation for secondary causes of osteoporosis showed 25-OH vitamin D levels of 23 ng/mL (NL 30-100 ng/mL), TSH 1.72 uIU/mL (NL 0.28-3.8 uIU/mL), PTH 19 pg/mL (NL 14-64 pg/mL), calcium 9.7 mg/dL (NL 8.7-10.7 mg/dL), phosphorus 4 mg/dL (NL 2.5-4.5 mg/dL), tryptase 4 mcg/L (NL <11 mcg/L), alkaline phosphatase 111 U/L (NL 30-115 U/L) and 24-hour urine calcium 168 mg (NL 100-300 mg). Urine immune electrophoresis and serum immunofixation did not show any evidence of monoclonal gammopathy. DEXA scan showed low BMD with Z-score of −4.4 SD in lumbar spine -3.1 in femoral neck. She was diagnosed with PAO. She stopped breast feeding after the diagnosis. As the bone mineral density was very low, she was started on teriparatide along with calcium and vitamin D supplementation. One year after treatment initiation, her DEXA scan showed improved bone mineral density with Z-score of −3.5 in lumbar spine and −1.9 in femoral neck. Her osteoporosis is currently being managed with teriparatide with plan to continue for a total duration of 24 months. Conclusion: PAO is under-recognized and under-reported, with limited available evidence on the management. Spontaneous improvement in BMD is known to occur in 6-12 months after pregnancy and lactation have been completed, although, the addition of anti-resorptive treatment in this setting may result in superior BMD gain compared with calcium and vitamin D supplementation alone. Use of teriparatide has shown to have significant increase in BMD and help with pain relief in PAO. Teriparatide has helped with improving the BMD in our patient. Nevertheless, controlled trials are lacking, and the optimal timing of teriparatide use in these women remains uncertain. Presentation: Thursday, June 15, 2023

Retrospective analyses of clinical features in 28 Chinese patients with type V osteogenesis imperfecta: new perspectives in an old issue

SummaryType V osteogenesis imperfecta (OI) is a form of OI characterized by radial head dislocation (RHD), calcification of interosseous membrane (CIM), and hyperplastic callus (HPC). In this study, we characterized the clinical features of 28 type V OI patients. We presented that dysfunctions of elbow, hip joint, and abnormal epiphyseal growth plate were associated with ectopic calcification and summarized the history of HPC progression and treatment.IntroductionThe current study aims to systematically characterize the skeletal phenotypes of patients with type V OI and suggested possible surgical solutions.MethodsA total of 28 patients were admitted for inpatient care at The Hong Kong University-Shenzhen Hospital diagnosed with type V OI (either clinically diagnosed or genetically confirmed with the IFITM5 c.-14C > T mutation).ResultsPrevalence of type V radiological features was comparable to previous literatures (RHD, 100%; CIM, 100%; HPC, 44%; and scoliosis, 50%). Novel skeletal phenotypes were presented including extension of coronoid process, acetabular labrum, acetabular protrusion, spontaneous autofusion of the hip, bulbous epiphysis, and popcorn calcification. Significant increase in BMD was observed in patients with bisphosphonate treatment. Twenty-five percent (3/12) of patients with preoperative use of indomethacin developed HPC postoperatively, and HPCs were absorbed in 2 young patients 2 years later.ConclusionThis retrospective study summarized the clinical features and highlighted the abnormalities in elbow, hip joint, and growth plate in type V OI patients. Our study contributed to a more comprehensive clinical spectrum of type V OI. We also characterized the natural progression of HPC formation and resorption in patients in different ages. The use of bisphosphonate treatment is effective in improving bone mineral density in type V OI patients, and whether indomethacin can reduce incidence of HPC formation deserves further investigation.

Effect of androgen deprivation therapy on bone mineral density in patients with prostate cancer.

Objectives:To access the effects of acute and chronic Androgen Deprivation Therapy on Bone Marrow Density and related bone markers; to compare the bone loss among the patients who terminated GnRH use and control group (not given ADP therapy at all) with the ones with acute or chronic Androgen Deprivation Therapy.Methods:A cross-sectional study was conducted in the Oncology Department of Nishtar Medical University & Hospital Multan for one year. Bone mineral density of the entire body, 1/3rd distal radius, ultra-distal forearm, femoral neck, and lumbar spine, was measured in 40 patients diagnosed with non-metastatic prostate cancer at baseline for the duration of six months. They were categorized into four groups: (i) acute ADT (less than six months of treatment; (ii) chronic ADT (greater than six months of treatment; (iii) former ADT; and (iv) no ADT (placebo groups). Quantitative measures of bone metabolism marker, including C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) was done.Results:The cross-sectional analysis showed that BMD dropped significantly in more in patients with former ADT or control groups as compared to chronic ADT. At the 6th month assessment, a significant decline in ultra-distal forearm BMD was demonstrated in patients from both acute and chronic ADT groups (4.05% and 2.54%, P = .001 and .016, respectively). Total body BMD was significantly reduced among those on acute treatment (2.91%, p=0.022). In the former ADT group, a significant increase of BMD was observed in the femoral neck and lumbar spine bones (1.60 % and 2.85%, P = .001 and .0064, respectively). The difference of changes in BMD of the acute and chronic groups was not significant. The levels of PINP and CTX levels were significantly increased in an chronic and acute group than in placebo or former ADT groups.Conclusion:Chronic and acute ADT users experience similar changes in BMD levels but reversibility of BMD can be achieved on withdrawal of treatment. Similarly disturbed bone metabolism markers come back in range on withdrawal of treatment.

Bone mineral density in postmenopausal women with osteoarthritis of knee joint

Objective. Study the state of mineral bone density (BMD) in postmenopausal women with osteoarthritis (OA) of the knee joint depending on the X-ray stage.Materials and methods. The study included 56 women between 44 and 75 years of age. The diagnosis of OA is established according to the diagnostic criteria of the American College of Rheumatology (ACR, 1991). For comparative analysis, patients were divided into two groups, taking into account the radiological stage: the 1st with 38 women with I–II radiology stage, the 2nd with 18 patients with III–IV radiology stage. The X-ray of the knee joint in the anterior projection is performed in a fixed bending position using a special frame (SynaFlexer TM Plexiglass positioning frame, Synarc Inc., USA). The BMD is estimated by a two-energy X-ray absorption technique in the femoral neck and lumbar spine.Results. Osteopenic syndrome is diagnosed in 52 (92.8%) of the total number of patients, 27 (48.2%) have osteopenia and 25 (44.6%) have osteoporosis. Four women (7.1%) have a normal BMD. There is no statistically significant difference in the frequency of detection of the osteopenic syndrome between the groups studied (p > 0.050). Statistically significant increases in BMD and T-criteria have been found as the OA progresses in both the femoral neck and the lumbar spine. The correlation analysis results show a significant positive correlation between the BMD femoral neck and the OA X-ray stage (r = 501; p < 0.001).Conclusions. The data show the presence of the osteopenic syndrome in the vast majority in postmenopausal women with OA of the knee joint. The high BMD values of the femur neck and lumbar spine are associated with the late X-ray stages of the OA of the knee joint.

Effect of Aerobic Exercises in Prevention of Bone Mass Loss Post Bariatric Surgeries

Background: Patients who have been submitted to bariatric surgery are prone to bone mass abnormalities caused by restriction of calcium intake associated with malabsorption of both calcium and vitamin D. Reduced calcium absorption is secondary to the exclusion of duodenum and proximal jejunum where calcium is maximally absorbed. Aerobic weight bearing exercise is more adapted to improve bone mass over whatever viable physical activity, they assume a double part over stressing the bones as they set both gravitational and muscular stress on bones. Objective: To determine the effect of aerobic exercises in prevention of bone mass loss post bariatric surgeries. Patients and Methods: Thirty female patients with post bariatric surgeries participated in this, their ages were between 25 to 45 years selected from Shebin El-Kom Hospital, Menoufia and randomly distributed into two equal groups: Group A (Study group): included 15 patients who received 30 minutes of aerobic exercise through walking on treadmill, in addition to conventional medical care 3 days per week and group B (Control group): included 15 patients who were on their conventional medical care. Results: There was no significant difference in T score of spine (L2-L4), femoral neck and total femur between both groups pre-treatment (p > 0.05). Comparison between both groups post treatment revealed a significant increase in T score of spine (L2-L4), femoral neck and total femur of the study group compared with that of the control group (p > 0.001). Conclusion: It can be concluded that aerobic exercises had fruitful effects in cases of osteoporosis patients after bariatric surgery as evidenced by the significant increase in BMD and T-score mean, so decrease risk of fractures and enhance physical performance.

Effect of Aerobic Exercises in Prevention of Bone Mass Loss Post Bariatric Surgeries

Background: Patients who have been submitted to bariatric surgery are prone to bone mass abnormalities caused by restriction of calcium intake associated with malabsorption of both calcium and vitamin D. Reduced calcium absorption is secondary to the exclusion of duodenum and proximal jejunum where calcium is maximally absorbed. Aerobic weight bearing exercise is more adapted to improve bone mass over whatever viable physical activity, they assume a double part over stressing the bones as they set both gravitational and muscular stress on bones. Objective: To determine the effect of aerobic exercises in prevention of bone mass loss post bariatric surgeries. Patients and Methods: Thirty female patients with post bariatric surgeries participated in this, their ages were between 25 to 45 years selected from Shebin El-Kom Hospital, Menoufia and randomly distributed into two equal groups: Group A (Study group): included 15 patients who received 30 minutes of aerobic exercise through walking on treadmill, in addition to conventional medical care 3 days per week and group B (Control group): included 15 patients who were on their conventional medical care. Results: There was no significant difference in T score of spine (L2-L4), femoral neck and total femur between both groups pre-treatment (p > 0.05). Comparison between both groups post treatment revealed a significant increase in T score of spine (L2-L4), femoral neck and total femur of the study group compared with that of the control group (p > 0.001). Conclusion: It can be concluded that aerobic exercises had fruitful effects in cases of osteoporosis patients after bariatric surgery as evidenced by the significant increase in BMD and T-score mean, so decrease risk of fractures and enhance physical performance.

Quantitative Ultrasound - An Epidemiological Tool to Uncover the Influence of Lifestyle Factors & its Associated Co Morbidities on Bone Density

Osteoporosis, the metabolic disorder has become a global epidemic1 with increase in life expectancy and changing life style. Quantitative ultrasound is a cheap, non invasive, portable and convenient method to estimate bone strength without any radiation hazard.2–5 The aim of our study is to estimate the bone mineral density by using quantitative ultrasound, look for the influence of parameters like lifestyle factors, comorbidities, chronic drug intake, and other risk factors on BMD; and compare the results with those in the literature done with DEXA scans. In our study of 516 subjects, (i) BMD measures varied from -5.6 to +.5.55 with a mean of -1.8. (ii) BMD decreased significantly with age (r=.351, p<0.0001), (iii) Low BMD was associated with increase in Fragility fractures (p=.007) (iv) Antacid intake, which was pretty common in our subjects (28.7%) led to decrease in BMD (p<.005). (v) Diabetes significantly reduced BMD (p<.005). (vi) Increase in BMI led to significant increase in BMD (r=.166, p<.0001). (vii) BMD increased significantly with increase in physical activity (r=.148, p<.001). Most of the associations found in our study, except that with diabetes, were similar to those consistently associated with BMD as measured with DEXA scans.6–15 Our study suggests the use of Quantitative ultrasound as powerful epidemiological tool with similar outcome measures to DEXA scan without any radiation hazards.

The therapeutic efficacy of denosumab for the loss of bone mineral density in glucocorticoid-induced osteoporosis: a meta-analysis.

ObjectivePrevention of steroidal osteoporosis is an important issue. There is no clear consensus on the impact of anti-RANKL antibody (denosumab) on BMD in patients with glucocorticoid-induced osteoporosis (GIO). In this study, we aimed to evaluate the impact of denosumab on BMD loss in patients with GIO.MethodsA comprehensive systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Web of Science and Google Scholar were used to search for original studies reported about BMD in patients with GIO treated with denosumab. In meta-analysis of BMD, the mean difference in the rate of change from baseline and the 95% CI were calculated using the random effects model. The mean differences in patients treated with denosumab were compared with those in patients treated with bisphosphonates.ResultsOut of 713 studies identified, seven studies met the selection criteria for the meta-analysis. At 6 and 12 months of denosumab therapy, increases in BMD were observed in the lumbar spine (2.99% [95% CI 2.71, 3.28] and 4.59% [95% CI 4.17, 5.01]), total hip (1.34% [95% CI 0.64, 2.04] and 2.16% [95% CI 2.05, 2.27]) and femoral neck (0.12% [95% CI −0.38, 0.62] and 1.55% [95% CI 0.45, 2.65]). Additionally, denosumab resulted in significant increases in BMD in the lumbar spine and femoral neck at 12 months compared with bisphosphonate therapy.ConclusionPatients with GIO experienced significant increases in BMD in response to treatment with denosumab that were detected in the lumbar spine, total hip and femoral neck at 12 months.

Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in post-menopausal women with osteoporosis and a high prevalence of secondary risk factors in real-life setting of a metabolic bone clinic; effect of age and vitamin D status

ABSTRACTPurpose: Teriparatide (TPD) is a skeletal anabolic agent used in patients with severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who are at hish risk of fracture. Predictors of therapeutic response to teriparatide in real-life setting are not well characterised. We investigated potential factors associated with teriparatide response in post-menopausal women with established osteoporosis.Methods: We carried out a retrospective survey of 48 women, aged 73.2 [7.5] years with severe osteoporosis and prevalent fractures treated with TPD according to the NICE criteria. BMD was measured at baseline, 6-12 and 18-24 months at the lumbar spine (LS), total hip (TH) and femoral neck (FN). Bone turnover markers, serum 25 (OH)vitamin D were determined at 3-12 and 12-24 months.Results: BMD increased at 6-12 months (% change mean [SEM] 6.5 [1.1] p = 0.004) and 18-24 months (8.45 % [1.2] p<0.001) at the LS. A significant increase in BMD was observed at FN (3.1 [1.3] % p = 0.02). Changes in BMD at the TH was higher in patients younger than 73 years compared to older women (% change in BMD 4.13 [1.64] % v/s -1.7 [1.1] p = 0.007). Baseline 25 (OH) vitamin D correlated with change in P1NP at 3-12 months (r = 0.45 p = 0.049).Conclusions: TPD-induced changes in BMD at the TH appears may be dependent on age. Vitamin D status may influence the early anabolic effect to TPD. Our data suggest that these factors may be important considerations when initiating and optimising treatment with TPD, although further larger studies are needed to confirm these findings.

The effect of levetiracetam on rat bone mineral density, bone structure and biochemical markers of bone metabolism

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals.Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing.We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group.The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings.

EFFECT OF A 5-YEAR ALFACALCIDOL TREATMENT IN COMBINATION WITH CALCIUM CARBONATE ON BONE MINERAL DENSITY IN THE PRIMARY FORMS OF SYSTEMIC OSTEOPOROSIS IN MEN

The article presents the results of 5-year treatment with a combination of alfacalcidol and calcium carbonate in 47 men with primary forms of systemic osteoporosis. The obtained results show the effectiveness of this treatment in patients with low and normal turnover forms of osteoporosis. Significant increase of BMD at L1-L4 was observed after the first year of treatment, at the Neck region - after 3-rd year of treatment. Comparison of the magnitude of the annual increase of BMD has shown that the effectiveness of the treatment increases with its duration. The possibility of hypercalcemia was excluded by monitoring of calcium levels in blood and urine at intervals of 3-6 months throughout the treatment period.

Efficiency of Ibandronate in Monotherapy and in Combination with Alfacalcidol in Women with Postmenopausal Osteoporosis

The aim of this study was to carry out a comparative analysis of the efficiency of ibandronate monotherapy and combined therapies with ibandronate and alfacalcidol in women with postmenopausal osteoporosis. Materials and Methods: A total of 53 women (mean age 60.7 years) with postmenopausal osteoporosis (PMO) were randomized to monotherapy with ibandronate 150 mg/month (Group Ib) (n=25) and therapy with ibandronate 150 mg/month plus alpha-D 3 (AD3) 1μg (alfacalcidol) daily (Group Ib+AD3) (n=28). All women received calcium and vitamin D 3 supplements. Patients were recruited in one center and were followed up for 6 months on a monthly basis. To assess the efficacy of therapy, BMD was measured at LS (L1–L4) and PF at the beginning and end of therapy by DEXA. Biochemical markers of bone turnover were also assessed. Results: Statistically significant increases in BMD compared with baseline values and the control group were observed in both ibandronate treatment groups. Growth of BMD was significantly higher in Group Ib+AD3 compared to Group Ib. An assessment of CTX dynamics showed a notable decrease in CTX level in patients of both groups compared with levels before treatment. Generally, PTH level decreased insignificantly, but a more pronounced reduction was seen in Group Ib+AD3. TP1NP level significantly increased in Group Ib and was more pronounced in Group Ib+AD3. Conclusion: Combined therapy with ibandronate sodium and the D-hormone analog alfacalcidol augments the effectiveness of treatment observed in ibandronate sodium monotherapy in PMO women. (Int J Biomed. 2016;6(3):190-194.).

Anti-sclerostin – is there an indication?

Several decades ago, a clinical condition that included severe bone overgrowth was described in a few patients in South Africa. The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. This protein is produced by osteocytes and exerts its effect as an inhibitor of bone formation by blocking the Wnt signaling pathway. By the use of a monoclonal antibody that can block sclerostin a novel therapeutic pathway for rebuilding bone has been described. Preclinical studies have shown increased bone mass following subcutaneously administered anti-sclerostin antibody in animals with induced postmenopausal osteoporosis as well as in intact male rats and non-human primates. In a phase II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg was given subcutaneously monthly or every three months and compared to 70 mg of oral alendronate given once a week or 20 μg of teriparatide subcutaneously once daily. All dose levels of romosozumab were associated with significant increase in BMD with the most pronounced gain in the group receiving 210 mg where lumbar spine BMD increased with 11.3% from baseline. The BMD for the placebo group decreased by 0.1% while the alendronate group increased 4.1% and the teriparatide increased 7.1%. Biochemical markers revealed a transitory increase in the bone formation marker P1NP while no change in the bone resorption marker β-CTX. In comparison, teriparatide resulted in an increase for both P1NP and β-CTX for the complete study period. Even though the rapid gain in BMD is promising when considering a treatment option for osteoporosis and other conditions with bone loss, there are so far no published studies on whether anti-sclerostin can reduce the number of fractures. Wnt signaling might also play an important role in fracture healing with substances that causes an upregulation of the Wnt pathway producing enhancement of the fracture healing process. Healing of experimental fractures in various animal models have shown improvement following subcutaneously administered anti-sclerostin antibody. While there are no published reports on the potential effect of systemically administered anti-sclerostin antibodies on fracture healing in humans.

Thrombin receptor deficiency leads to a high bone mass phenotype by decreasing the RANKL/OPG ratio

Thrombin and its receptor (TR) are, respectively, expressed in osteoclasts and osteoblasts. However, their physiological roles on bone metabolism have not been fully elucidated. Here we investigated the bone microarchitecture by micro-computed tomography (μCT) and demonstrated increased trabecular and cortical bone mass in femurs of TR KO mice compared to WT littermates. Trabecular thickness and connectivity were significantly enhanced. The physiological role of TR on both inorganic and organic phases of bone is illustrated by a significant increase in BMD and a decrease in urinary deoxypyridinoline (DPD) crosslink concentration in TR KO mice. Moreover, TR KO cortical bone expanded and had a higher polar moment of inertia (J), implying stronger bone. Bone histomorphometry illustrated unaltered osteoblast and osteoclast number and surface in femoral metaphyses, indicating that thrombin/TR regulates osteoblasts and osteoclasts at functional levels. Serum analysis showed a decrease in RANKL and an increase in osteoprotegerin (OPG) levels and reflected a reduced RANKL/OPG ratio in the TR KO group. In vitro experiments using MC3T3 pre-osteoblasts demonstrated a TR-dependent stimulatory effect of thrombin on the RANKL/OPG ratio. This effect was blocked by TR antagonist and p42/p44-ERK inhibitor. In addition, thrombin also intensified p42/p44-ERK expression and phosphorylation. In conclusion, the thrombin/TR system maintains normal bone remodeling by activating RANKL and limiting OPG synthesis by osteoblasts through the p42/44-ERK signaling pathway. Consequently, TR deficiency inhibits osteoclastogenesis, resulting in a high bone mass phenotype.

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).

PurposeTo systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).Materials and methodsMedline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.ResultsOf the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood–lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication).ConclusionFindings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk–benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

The effect of tocilizumab on bone mineral density in patients with methotrexate-resistant active rheumatoid arthritis

The aim of this study was to analyse the effects of therapy with tocilizumab (TCZ), an anti-IL-6 receptor antibody, on BMD of the lumbar spine and femoral neck in patients with RA. Eighty-six patients with active RA (indicated by a 28-joint DAS ESR >3.2) despite treatment with MTX 12 mg/week were included in this open-label prospective study and started on TCZ (8 mg/kg every 4 weeks). All patients used a stable dosage of MTX and were not allowed to use steroids or bisphosphonates during the study period. BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry at baseline and 52 weeks after initiating TCZ. Seventy-eight patients completed this study. BMD of the lumbar spine and femoral neck remained stable after 1 year of TCZ treatment. In 33 patients who had osteopenia at baseline, there was a significant increase in BMD of the lumbar spine [mean 0.022 (s.d.) 0.042, P < 0.05] and femoral neck [0.024 (0.0245), P < 0.05]. TCZ affects BMD in patients who had active RA despite treatment with MTX. BMD of the lumbar spine and femoral neck in patients with normal BMD at baseline was stable. TCZ increased the BMD of patients who had osteopenia at baseline.

Prevention of bone loss and vertebral fractures in patients with chronic epilepsy—Antiepileptic drug and osteoporosis prevention trial

To evaluate whether use of a bisphosphonate (risedronate) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs (AEDs) long term can prevent the loss of bone mass (BMD, bone mineral density) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures. Antiepileptic drug and osteoporosis prevention trial (ADOPT) was designed as a prospective 2-year double-blind, randomized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin, phenobarbital, sodium valproate, or carbamazepine for a minimum of 2 years. All enrolled participants received calcium and vitamin D supplementation, and were randomized to risedronate or matching placebo. Total body, bilateral proximal femora, and anteroposterior (AP) lumbar spine BMDs in addition to morphometric lateral vertebral assessments (LVAs) were evaluated by a dual energy x-ray absorptiometry (DXA) instrument. Comparisons of BMDs were made between baseline, 1 year, and after 2 years of enrollment in the study. The incidence of new vertebral and nonvertebral fractures was secondary end point. Of the 80 patients initially enrolled in the study, 53 patients completed the study. Baseline characteristics of the two groups were similar. At the end of the study, in the placebo plus calcium and vitamin D group, we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69% (18/26) of the participants. In the risedronate plus calcium and vitamin D group, we observed significant improvement of BMDs in 70% (19/27) of the participants. At the end of the study, the risedronate group experienced a significant increase of BMD at the lumbar spine L1-4 (1.267-1.332 g/cm(2)), which was significantly larger than that seen in the placebo group) (1.229 g/cm(2) vs. 1.245 g/cm(2) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora. Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group. Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69% of male veterans with epilepsy who were taking AEDs. In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group, which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort.

Assessing the effect of baseline status of serum bone turnover markers and vitamin D levels on efficacy of teriparatide 20 μg/day administered subcutaneously in Japanese patients with osteoporosis

In this previously reported multicenter study, teriparatide 20μg/day was administered to elderly Japanese subjects (93% female; median age 70years) with osteoporosis and at high risk of fracture during a 12-month, randomized, double-blind, placebo-controlled period, which was followed by a 12month treatment period in which all subjects received open-label teriparatide. Subjects were randomized 2:1 to teriparatide versus placebo (teriparatide n=137, placebo-teriparatide n=70). This was an exploratory analysis to determine whether the baseline status of serum bone turnover markers (BTMs) and vitamin D levels affect the efficacy of teriparatide at 20μg/day. The BTMs included were type I procollagen N-terminal pro-peptide (P1NP) and type I collagen cross-linked C-telopeptide (CTX). Changes in BMD were analyzed by subgroups: (1) tertile subgroups of BTM; (2) BTM determined by the upper limit of normal; and (3) level of vitamin D. Teriparatide increased lumbar spine BMD in all subgroups by 10% or more through 24months. Subgroups with higher baseline BTM levels had greater mean percent changes of lumbar spine BMD through 24months. The baseline status of vitamin D sufficiency did not impact the mean percent change of lumbar spine BMD through 24months. Results of this study suggest that clinically significant increases in BMD can be achieved in patients receiving teriparatide regardless of baseline BTM or vitamin D levels. Additionally, when vitamin D is coadministered, vitamin D insufficiency would not be expected to affect the overall efficacy of teriparatide.

A synergistic bone sparing effect of curcumin and alendronate in ovariectomized rat

The purpose of this study was to evaluate the therapeutic effects of combination therapy with curcumin and alendronate on bone remodeling after ovariectomy in rats. Eighty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed amongst four groups: untreated OVX group, curcumin-administered group, alendronate-administered group, and the combination therapy group. At 8 and 12 weeks after surgery, rats from each of the groups were euthanized. Serum biochemical markers of bone turnover, including osteocalcin and alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX) were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test. Serum biochemical markers of bone turnover in the experiment groups (curcumin administered group, alendronate administered group, and the combination therapy group) were significantly lower than in the untreated OVX group (p < 0.05). The combination therapy group had lower ALP and CTX-1 concentrations at 12 weeks, which were statistically significant compared with the curcumin only and the alendronate only group (p < 0.05). The combination therapy group had a significant increase in BMD at 8 weeks and Cr.BMD at 12 weeks compared with the curcumin-only group (p = 0.005 and p = 0.013, respectively). The three point bending test showed that the 4th lumbar vertebrae of the combination therapy group had a significantly greater maximal load value compared to that of the curcumin only and the alendronate only group (p < 0.05). The present study demonstrated that combination therapy with a high dose of curcumin and a standard dose of alendronate has therapeutic advantages over curcumin or alendronate monotherapy, in terms of the synergistic antiresorptive effect on bone remodeling, and improving bone mechanical strength.

Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: The OCEAN study

Osteoporosis occurs when there is an imbalance between resorption and formation of bone, with resorption predominating. Inhibitors of cathepsin K may rebalance this condition. This is the first efficacy study of a new cathepsin K inhibitor, ONO-5334. The objective of the study was to investigate the efficacy and safety of ONO-5334 in postmenopausal osteoporosis. This was a 12-month, randomized, double-blind, placebo- and active-controlled parallel-group study conducted in 13 centers in 6 European countries. Subjects included 285 postmenopausal women aged 55 to 75 years with osteoporosis. Subjects were randomized into one of five treatment arms: placebo; 50 mg twice daily, 100 mg once daily, or 300 mg once daily of ONO-5334; or alendronate 70 mg once weekly. Lumbar spine, total hip, and femoral neck BMD values were obtained along with biochemical markers of bone turnover and standard safety assessments. All ONO-5334 doses and alendronate showed a significant increase in BMD for lumbar spine, total hip (except 100 mg once daily), and femoral neck BMD. There was little or no suppression of ONO-5334 on bone-formation markers compared with alendronate, although the suppressive effects on bone-resorption markers were similar. There were no clinically relevant safety concerns. With a significant increase in BMD, ONO-5334 also demonstrated a new mode of action as a potential agent for treating osteoporosis. Further clinical studies are warranted to investigate long-term efficacy as well as safety of ONO-5334.