Increase In Spine Bone Mineral Density Research Articles

The association between prediabetes and bone mineral density: A meta-analysis.

Prediabetes is an intermediate metabolic state between euglycaemia and diabetes, including three different definitions: impaired fasting glucose, impaired glucose tolerance, and mildly elevated glycated haemoglobin (HbA1c) (range 5.7%-6.4%). The effect of prediabetes on bone mineral density (BMD) has not been established. Therefore, we performed a meta-analysis to evaluate the association between prediabetes and BMD. We retrieved studies related to prediabetes and BMD from PubMed, Web of Science, and Embase databases from January 1990 to December 2022. All data were analysed using the random effects model. Statistical heterogeneity was tested by I2 . Subgroup analysis was performed after each study-level variable was pre-defined by meta-regression. A total of 17 studies were included involving 45,788 patients. We detected a significant overall association of prediabetes with increased spine BMD (weighted mean difference [WMD]=0.01, 95% CI [0.00, 0.02], p=0.005; I2 =62%), femur neck (FN) BMD (WMD=0.01, 95% CI [0.00, 0.01], p<0.001; I2 =19%), and femur total (FT) BMD (WMD=0.02, 95% CI [0.01, 0.03], p<0.001; I2 =51%). Several variables leading to heterogeneity were defined by meta-regression, including age, sex, region, study type, dual-energy X-ray absorptiometry scanner manufacturer, and prediabetes definition. Subgroup analyses indicated that the association of prediabetes with increased BMD was stronger in men, Asians, and older adults over 60years of age. Current evidence shows that prediabetes is strongly associated with increased BMD of the spine, FN, and FT. The association was stronger among males, Asians, and older adults over 60years of age.

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103)

Background and objectivesADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methodsThirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. ResultsAfter 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. ConclusionsTwo years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.

The Real-World Effect of 12 Months of Romosozumab Treatment on Patients With Osteoporosis With a High Risk of Fracture and Factors Predicting the Rate of Bone Mass Increase: A Multicenter Retrospective Study.

ABSTRACTExcluding clinical trials, there is limited evidence on the effect of 12 months of romosozumab treatment on bone mineral density (BMD) increase in real‐world clinical practice because its use has only been approved recently. Thus, this study aimed to investigate the real‐world effect of 12 months of romosozumab treatment on BMD increase and identify factors that predict the rate of BMD increase after 12 months of romosozumab treatment. We retrospectively investigated 106 patients who completed a 12‐month romosozumab treatment for osteoporosis with a high risk of fractures at four hospitals from March 2020 to March 2022. The univariate and multiple regression analyses were performed to analyze the concurrent effects of various factors on the BMD increase after the 12‐month romosozumab treatment. After 1 year of treatment, the lumbar spine BMD increased by 14.6%, and femoral neck BMD increased by 5.1%. Univariate regression analysis found that male sex, high tartrate‐resistant acid phosphatase 5b (TRACP‐5b) value before romosozumab administration, absence of osteoporosis medications before romosozumab administration, and low baseline lumbar spine BMD were associated with the extent of lumbar spine BMD increase. Moreover, stepwise multiple regression analysis found that the TRACP‐5b value before romosozumab administration was a significant predictor of the rate of lumbar spine BMD increase after 1 year of romosozumab administration. In conclusion, our results demonstrated the effectiveness of the 12‐month romosozumab treatment for osteoporosis with a high risk of fractures and the TRACP‐5b value before romosozumab administration was a significant predictor of the rate of lumbar spine BMD increase after 1 year of romosozumab administration. Our findings could help establish more efficient treatment strategies for patients with osteoporosis at a high risk of fracture. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103)

Background and objectivesADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methodsThirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. ResultsAfter 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. ConclusionsTwo years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Trial.

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n= 33), 12 months of risedronate ("Risedronate") (n= 33), or double placebo ("Placebo") (n= 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p= 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p< 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p< 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The spine, particularly its trabecular component as measured by lateral spine dual-energy x-ray absorptiometry (DXA), is most severely affected. Low BMD and bone formation are associated with relative insulin-like growth hormone-1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with off-label recombinant human (rh)IGF-1 followed by antiresorptive therapy with risedronate would increase BMD more than risedronate alone or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD) (Z- or T-score <-1.0). Participants were randomized to 1 of 3 groups: 6 months of rhIGF-1 (starting dose 30 mcg/kg SQ BID) followed by 6 months of risedronate (35mg PO weekly) (“rhIGF-1/Risedronate”) (n=33), 12 months of risedronate (35mg PO weekly) (“Risedronate”) (n=33), or double placebo (“Placebo”) (n=16). Participants received calcium 1200 mg and vitamin D 800 IU daily. rhIGF-1 was titrated to maintain IGF-1 levels within the age-adjusted normal range. Main outcome measures were aBMD at the spine [1° endpoint: postero-anterior (PA) spine BMD], hip, and radius by DXA, and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by multi-detector computed tomography (MDCT) or high-resolution peripheral quantitative CT (HR-pQCT). At baseline, mean age [28 ± 7 y (mean ± SD)], BMI (18.5 ± 1.9 kg/m2), and BMD were similar among groups. At 12 months, mean PA spine aBMD was higher in the rhIGF-1/Risedronate (p=0.03), and trended towards being higher in the Risedronate (p=0.08), group than the Placebo group. Mean lateral spine aBMD was higher in the rhIGF-1/Risedronate than either the Risedronate (p=0.002) or Placebo (p=0.04) groups. From baseline to 12 months, mean PA and lateral spine aBMD increased by 1.9 ± 0.6% and 4.2 ± 1.0% in the rhIGF-1/Risedronate (p<0.05), 1.7 ± 0.8% and 1.7 ± 1.0% in the Risedronate (p=NS), and decreased by 0.3 ± 0.8% and 1.1 ± 1.3% in the Placebo (p=NS), groups, respectively. Areal BMD Z-scores did not normalize in any group. At 12 months, vertebral vBMD by MDCT was higher (p<0.05), and vertebral strength trended towards being higher, in the rhIGF-1/Risedronate than Placebo group. Neither hip or radial BMD, nor radial or tibial estimated strength, by HR-pQCT differed among groups. rhIGF-1 was well tolerated. In conclusion, sequential therapy of 6 months of rhIGF-1 followed by 6 months of risedronate increased lateral spine aBMD, the site most severely affected in women with anorexia nervosa, more than risedronate or placebo. These data suggest that strategies that are anabolic and antiresorptive to bone may be most effective in increasing BMD in women with anorexia nervosa.

A 3-Week Tryptophan-Deficient Diet Resulted in Decreased Body Weight and Increased Trabecular Bone Mass in Mice

Tryptophan is an essential amino acid with a variety of bioactive metabolites including serotonin, melatonin and nicotinamide. Dietary Trp restriction results in increased lifespan but with detrimental side effects. The initial catabolite in the Trp breakdown pathway, kynurenine, increases with aging and induces bone loss. Thus, we hypothesized that eliminating Trp in the diet of older mice might be osteoprotective. In an IACUC-approved protocol, we fed either 0, 0.2 (standard), 0.7 or 1.25% Trp-containing diets to aged (23-month-old) C57BL/6 mice for a planned eight weeks. There was a rapid decrease in body weight in the mice fed the 0% tryptophan diet and the mice had to be sacrificed at three weeks (25.2±1.4 vs 35.4±3.6 vs 33.9±2.4 vs 33.4±3.1 gm, (Means+SD, No Trp: 0%; Standard Trp 0.2%; High Trp: 0.7%; High Trp: 1.25%, p=0.0004, 0 vs 0.2%, n=9-10/group). Removal of Trp from the diet had a differential effect on bone mineral density (BMD). Total BMD was increased in the low Trp group: (0.0548±0.0017 vs 0.518±0.0021 vs 0.0526±0.0021 vs 0.0524±0.0022, Means+SD, No Trp: 0%; Standard Trp 0.2%; High Trp: 0.7%; High Trp: 1.25%, p=0.016, 0 vs 0.2%). Femoral BMD did not change; however, spinal BMD rose (0.0603±0.005 vs 0.0477±0.06 vs 0.0505±0.005 vs 0.0535±006; Means+SD, Trp 0% vs 0.2%, p=0.00009). The mice on the 0% Trp diet also had lower body fat (22.4±2.3% vs 26.7±3.3%; Means+SD, Trp 0 vs 0.2%, p=0.005). Thus, dietary Trp restriction resulted in a beneficial increase in spinal BMD, though at least in part related to weight loss.

Combined effect of teriparatide and an anti-RANKL monoclonal antibody on bone defect regeneration in mice with glucocorticoid-induced osteoporosis.

The purpose of this study was to examine the effect of single or combination therapy of teriparatide (TPTD) and a monoclonal antibody against the murine receptor activator of nuclear factor κB ligand (anti-RANKL Ab) on cancellous and cortical bone regeneration in a mouse model of glucocorticoid-induced osteoporosis (GIOP). C57BL/6J mice (24weeks of age) were divided into five groups: (1) the SHAM group: sham operation+saline; (2) the prednisolone (PSL) group: PSL+saline; (3) the TPTD group: PSL+TPTD; (4) the Ab group: PSL+anti-RANKL Ab; and (5) the COMB group: PSL+TPTD + anti-RANKL Ab (n=8 per group). With the exception of the SHAM group, 7.5mg of PSL was inserted subcutaneously into mice, to generate a mouse model of GIOP. Four weeks after insertion, bone defects with a diameter of 0.9mm were created to assess bone regeneration on both femoral metaphysis (cancellous bone) and diaphysis (cortical bone). After surgery, therapeutic intervention was continued for 4weeks. Saline (200μl) or TPTD (40μg/kg) was injected subcutaneously five times per week, whereas the anti-RANKL Ab (5mg/kg) was injected subcutaneously once on the day after surgery. Subsequently, the following analyses were performed: microstructural assessment of bone regeneration and bone mineral density (BMD) measurement via micro-computed tomography, and histological, histomorphometrical, and biomechanical analyses with nanoindentation. The COMB group showed the highest lumbar spine BMD increase (vs. the PSL, TPTD, and Ab groups). The volume of regenerated cancellous bone at the bone defect site was higher in the COMB group compared with the PSL, TPTD, and Ab group. The volume of the regenerated cortical bone was significantly higher in the COMB group compared with the PSL group, and its hardness was significantly higher in the COMB group compared with the PSL and TPTD groups. In a mouse model of glucocorticoid-induced osteoporosis, the combination therapy of TPTD plus the anti-RANKL Ab increased bone mineral density in the lumbar spine and regenerated cancellous bone volume compared with single administration of each agent, and also increased regenerated cortical bone strength compared with single administration of TPTD.

Early changes in bone turnover predict longer-term changes in bone mineral density but not trabecular bone score in frail older women.

We sought to examine the association between shorter-term changes in markers of bone turnover and longer-term changes in bone mineral density (BMD) and microstructure in a cohort of frail elderly women with multiple comorbid conditions including osteoporosis. We performed a secondary analysis of a 2-year zoledronic acid trial for osteoporosis in 155 women residents of long-term care communities (mean age 86.9 years). We examined the association of the 6-month change in serum C-terminal crosslinking telopeptide of type I collagen (CTX) and serum intact procollagen type I N propeptide (PINP) with the 12- and 24-month changes in BMD at the spine and hip and the trabecular bone score (TBS), an indirect measure of bone microstructure. For every 0.2-ng/ml 6-month CTX decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.2% (p = 0.7210) and 1.1% (p = 0.0396), respectively; total hip BMD 1.1% (p = 0.0279) and 0.9% (p = 0.0716); and femoral neck BMD 1.7% (p = 0.0079) and 0.9% (p = 0.1698). Similarly, for every 20-ng/ml 6-month PINP decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.9% (p = 0.0286) and 1.4% (p = 0.0012), respectively; total hip BMD 1.4% (p = 0.0005) and 1.4% (p = 0.0006); and femoral neck BMD 2.3% (p < 0.0001) and 2.0% (p < 0.0001). Bone marker changes were not consistently associated with TBS changes. Shorter-term 6-month changes in bone turnover markers are associated with the long-term changes in BMD over 1-2 years in the spine and hip but not with TBS.

Comparison of efficacy and safety of teriparatide and hyaluronic acid - calcitonin combination treatments in Chinese osteoporotic patients with risk of bone fracture: A preliminary investigation

Purpose: To evaluate the efficacy and safety of teriparatide and hyaluronic-calcitonin combination treatment in Chinese osteoporotic patients with risk of bone fracture.Methods: Osteoporotic patients aged 30 to 80 years, with at least one vertebral fracture and immediate risk of new vertebral fractures, were recruited from Hangzhou First People's Hospital. They were randomly assigned to two groups (50/group) treated with either teriparatide (20 μg/day) or hyaluronic acid + calcitonin (1:1 ratio, 200 IU daily) for 12 months. The patients were followed up every 3 months. Bone mineral density (BMD) was evaluated using x-ray absorptiometry. The proportion of patients with new fractures was recorded. Changes in serum osteocalcin and serum bone alkaline phosphatase (BSAP) from baseline to endpoint were also measured.Results: Treatment with teriparatide at a dose of 20 μg/day resulted in a significant reduction in the proportion of patients with new fractures (p &lt; 0.05), when compared to patients treated with a combination of hyaluronic acid + calcitonin (200 IU daily). Teriparatide treatment for 12 months resulted in significant increase in lumbar BMD. Significant increases in spine BMD were evident after 3 months of treatment. There were significantly greater increases in serum osteocalcin and BSAP levels in teriparatide-treated patients than in those given hyaluronic acid + calcitonin. The most common treatment adverse event reported by both sexes was dizziness.Conclusion: These results demonstrate that teriparatide is efficacious and well tolerated in Chinese men and post-menopausal women with osteoporosis, when compared to the combination of hyaluronic acid and calcitonin. The efficacy of teriparatide is not associated with gender differences.&#x0D; Keyword: Teriparatide, Calcitonin, Hyaluronic acid, Bone-specific alkaline phosphatase, Postmenopausal, Bone mineral density

Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

ObjectiveClinical trial results have shown that, in glucocorticoid‐treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24.MethodsThis phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid‐initiating) or for ≥3 months (glucocorticoid‐continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid‐continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D.ResultsOf 795 patients, 590 (74.2%) completed the study (in the glucocorticoid‐initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid‐continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid‐initiating patients (24‐month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24‐month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid‐continuing patients (24‐month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24‐month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups.ConclusionDenosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid‐treated patients.

Denosumab effects on bone density and turnover in postmenopausal women with low bone mass with or without previous treatment.

Prior osteoporosis therapies may affect the skeletal response to denosumab. We compared the effect of denosumab (60 mg every 6 months for 12 months) on bone mineral density and bone metabolism parameters in postmenopausal women with low bone mass who were either treatment-naïve (n = 30), or previously treated either with zoledronic acid (n = 30), or teriparatide (n = 22). We assessed lumbar spine bone mineral density (BMD) and measured serum concentrations of the bone turnover markers pro-collagen type 1 N-terminal propeptide (PINP) and C-terminal-cross-linking telopeptide of type 1 collagen (CTX), as well as sclerostin, dickkopf-1 (Dkk-1), and myostatin. Lumbar spine BMD increased equivalently in all three groups after 12 months of denosumab compared to baseline (p < 0.001). Serum PINP and CTX decreased significantly with denosumab in pre-treated women reaching the same nadir levels as in treatment-naïve patients (p < 0.001). Women pre-treated with teriparatide displayed lower baseline myostatin concentrations as compared to the other two groups (p < 0.001). Changes in lumbar spine BMD in teriparatide pre-treated women correlated with changes in bone turnover markers and myostatin. Denosumab induced similar increases in lumbar spine BMD in treatment-naïve and pre-treated patients and suppressed serum PINP and CTX to the same levels regardless of prior treatments. In teriparatide pre-treated patients the magnitude of change in bone turnover markers is associated with BMD response.

Effect of increasing doses of vitamin D on bone mineral density and serum N-terminal telopeptide in elderly women: a randomized controlled trial.

There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.

Efficacy of Switching From Teriparatide to Bisphosphonate or Denosumab: A Prospective, Randomized, Open‐Label Trial

There is no consensus on an optimal treatment after daily teriparatide (TPTD). We performed a prospective, randomized, open-label, 12-month trial to investigate the efficacy of follow-up treatment after daily TPTD treatment for Japanese patients. Three-hundred patients were enrolled in this study. Patients received oral bisphosphonate (BP) including alendronate (ALN; 35 mg/week) and minodoronate (MINO; 50 mg/month), or subcutaneous denosumab (60 mg/6 month). The primary efficacy measure was bone mineral density (BMD) responses in the lumbar spine (LS) and femoral neck (FN). Lumbar spine BMD increased by 1.3 ± 5.1% in the ALN subgroups, 0.5 ± 4.6% in the MINO subgroups, and 4.3 ± 3.5% in the denosumab subgroups. Femoral neck BMD increased by 0.7 ± 4.6% in the ALN subgroups, 0.2 ± 4.6% in the MINO subgroups, and 1.4 ± 3.4% in the denosumab subgroups. Lumbar spine BMD increases were significantly greater in the denosumab subgroup than the BP subgroups. There were no significant differences in FN BMD increases among the three subgroups. Lumbar spine BMD increases were significantly greater in the denosumab subgroup than the BP subgroups, whereas FN BMD increases were not significant. Denosumab treatment was more effective in increasing BMD and therefore has the potential benefit of fracture prevention. Further research is warranted to determine the optimal treatment after daily TPTD. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review.

Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with bone fragility and increased fracture risk. However, little is known regarding the effect of anti-osteoporotic treatment on bone mineral density (BMD) and/or fracture risk in these patients. We aimed to systematically investigate the efficacy of anti-osteoporotic medications in patients with diabetes in comparison with non-diabetic subjects. MEDLINE and Scopus databases were searched (up to 31st October 2017). Nine studies fulfilled the pre-defined inclusion criteria [patients with T2DM (n = 8) or either T1DM or T2DM (n = 1)]. Regarding fracture risk, five studies were identified. Alendronate demonstrated comparable vertebral anti-fracture efficacy in patients with and without diabetes (n = 2), whereas non-vertebral fracture risk was either the same (n = 1) or higher in diabetic patients (n = 1). Raloxifene also demonstrated comparable vertebral anti-fracture efficacy in both groups (n = 2), without any effect on non-vertebral fractures in either group. In one study, diabetic patients exposed to raloxifene demonstrated the same vertebral and non-vertebral fracture risk with non-diabetic patients. Teriparatide (n = 1) demonstrated the same non-vertebral fracture rates in both patients with and without T2DM. Regarding BMD, equal increases in spine BMD were observed with alendronate (n = 4), risedronate (n = 1), and teriparatide (n = 1). With respect to hip BMD, similar increases were observed with teriparatide (n = 1), whereas data regarding alendronate were controversial (n = 3). No eligible study was found for zoledronic acid, ibandronate, strontium ranelate, denosumab, or bazedoxifene. The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.

Predictors of improvement in bone mineral density after celiac disease diagnosis.

Low bone density is frequently found in patients newly diagnosed with celiac disease (CD), and improvement is variable. This study was performed to assess changes in bone mineral density (BMD) by dual x-ray absorptiometry (DXA) at the lumbar spine, hip, and distal one-third radius as well as clinical predictors of BMD changes after the diagnosis and treatment of CD. Adult CD patients who had serial DXA at the Celiac Disease Center at Columbia University Medical Center were included (N = 103). We assessed within-person changes in BMD with paired t-tests. Multiple regression was utilized to assess baseline clinical and laboratory predictors of BMD improvement after diagnosis and treatment. The mean age of our sample was 45.6 years (±SD 15.1) and 60% were female. After a median follow-up of 21 months, lumbar spine BMD increased by 1.7 ± 5.5% (p = 0.006) after CD diagnosis. There was a similar trend at the total hip (1.6 ± 6.3%, p = 0.06), but no change at the femoral neck or distal one-third radius. Lower baseline serum calcium predicted a greater increase in lumber spine BMD (ß = -0.0470 g/cm2, p = 0.002). At the hip, higher baseline creatinine clearance (ß = 0.005, p = 0.02) was associated with greater gains in BMD. BMD increases at the lumbar spine after the diagnosis of CD and greater BMD improvement is associated with lower baseline serum calcium. This suggests that those with the lowest calcium, which is likely a surrogate for the greatest malabsorption, may have the greatest potential for improvement in skeletal health after treatment of CD.

Predictors of change of trabecular bone score (TBS) in older men: results from the Osteoporotic Fractures in Men (MrOS) Study.

Our objective was to compare and contrast predictors of changes in TBS, total hip BMD, and lumbar spine BMD. Our study population was 3969 Osteoporotic Fractures in Men (MrOS) cohort participants (mean age 72.8years) with repeat measures of TBS, lumbar spine and total hip BMD, body mass index (BMI) less than 37kg/m2, and no use of bisphosphonate or glucocorticoid medications. TBS was scored (Med-Imaps Software version 2.1) and BMD measured on Hologic densitometers. One thousand four hundred forty-four men had a TBS decrease >0.04units (estimated least significant change for TBS), 795 men had a TBS increase >0.04units, and 1730 men had TBS change ≤0.04units over mean follow-up of 4.6years. Older age was not associated with TBS change, but was associated with greater decline in lumbar spine and total hip BMD. Compared to stable weight, >10% weight loss was strongly associated with an increase in TBS [effect size =1.24 (95% CI 1.12, 1.36)] and strongly associated with a decrease in total hip BMD [-1.16 (95% CI -1.19, -1.03)]. Other predictors discordant for longitudinal changes of TBS and BMD included baseline BMI, walk speed, and ACE inhibitor use. Predictors of changes in TBS are different from predictors of changes in lumbar spine and total hip BMD. At least when assessed on Hologic densitometers, weight loss is associated with subsequent declines in spine and total hip BMD but subsequent increase in TBS. Faster walk speed may protect against loss of hip BMD, but is not associated with longitudinal changes of TBS.

Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial.

Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain. We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover. The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI -1.1% to 5.0%), 2.2% (95% CI -1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI -0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2-3 years in the 1-mg group, 3-4 years in the 2.5-mg group and at least 5 years in the 5-mg group. The antiresorptive activity of single zoledronate doses of 1-5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended. www.anzctr.org.au, no. ACTRN12607000576426.

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. NCT01751646.

Short-term daily teriparatide in patients with rheumatoid arthritis

Objective: The aim of this study was to compare the efficacy of six-month teriparatide treatment followed by six-month bisphosphonate therapy with 12-month bisphosphonate monotherapy in Japanese rheumatoid arthritis (RA) patients who had not been previously treated for osteoporosis.Methods: A total of 34 RA patients with osteoporosis were enrolled. Thirteen patients received six-month teriparatide prior to six-month minodronate therapy (PTH group), and 21 patients received 12-month minodronate therapy (BP group). Bone mineral density (BMD), and bone turnover markers were measured prior to and 6 and 12 months after the initiation of treatment.Results: Bone mineral density of the spine was significantly increased after 12 months of treatment in both groups. In the PTH group, the mean percent change of BMD of the spine was significantly higher at 12 months after the initiation of treatment, as compared to the BP group (PTH group: 9.9 ± 1.5%, BP group: 5.5 ± 0.7%). Femoral neck BMD was significantly increased only in the PTH group after 12 months.Conclusion: Therapy involving six-month teriparatide followed by six-month minodronate therapy increased spine BMD to a greater degree than 12-month minodronate monotherapy. The strategy of short-term administration of teriparatide for RA patients with osteoporosis might be useful when additional bisphosphonate therapy is considered.