Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women

Abstract

Purpose: This extended randomized prospective study aimed to compare the 4-year clinical outcomes of denosumab treatment alone or in combination with teriparatide in treatment-naïve postmenopausal Japanese patients with osteoporosis.

Methods: Between July 2013 and December 2016, 30 eligible women from our previous study were enrolled. After newly adding 17 randomly assigned patients, 47 patients were classified into the denosumab alone group (denosumab group, n?=?22) or denosumab plus teriparatide group (combination group, n?=?25). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I collagen (NTX), and bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at regular time points up to 48 months of treatment to determine percentage changes.

Results: BAP was significantly decreased from baseline in both groups from 24 to 48 months, with significant differences at all time points between the groups. TRACP-5b and urinary NTX were comparably decreased at every time point in both groups versus pretreatment levels. L-BMD was significantly more increased by combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs. 14.2% increase at 48 months). There were no significant differences in H-BMD between the groups, although levels tended to be higher in the combination group throughout the study period (9.7% increase vs. 6.8% increase at 48 months).

Conclusion: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.     

Effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density in patients with ophthalmologic disease treated with glucocorticoid

Abstract

Objectives. Glucocorticoid (GC) is usually used for the treatment of systemic inflammatory diseases. We performed the prospective study to clarify the effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic disorders for 12 months.

Methods. BMD was measured with dual-energy X-ray absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic indices.

Results. BMD values in the alendronate group were significantly higher than those in the alfacalcidol group during 12 months. Alendronate significantly reduced urinary NTX levels from the baseline during 12 months, although alfacalcidol did not affect them. Serum BAP levels in the alendronate group were significantly lower than those in the alfacalcidol group during 9 months. The effects of alendronate on BMD and NTx in male patients seemed to be somewhat potent compared with those in female patients.

Conclusions. Alendronate is effective to prevent BMD loss and bone resorption induced by GC treatment in patients with ophthalmic diseases without systemic disorders. There might be sex differences in the potency of alendronate effects.     

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.     

Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis: results of a phase II clinical trial

Osteoporosis is an important cause of morbidity in beta-thalassemia patients. Bisphosphonates have been recently used for the treatment of osteoporosis in beta-thalassemia. This study is a prospective quasi-experimental study to assess the efficacy and safety of zoledronic acid in thalassemics with osteoporosis. Eighteen thalassemia patients with osteoporosis were given zoledronic acid 4 mg intravenously every 3 months over a period of 12 months. The efficacy of treatment was assessed by measuring (BMD) at the lumbar spine, femoral neck, and hip at baseline, 6, and 12 months. Z-score was used to measure the BMD. Other medical assessments included markers of bone formation and resorption (bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline), and the assessment of pain score, analgesic score, and performance score. Ten thalassemic osteoporotic patients were followed up only with serial BMDs as controls. Both groups had no significant difference with respect to age, gender, and baseline BMD. Patients taking zoledronic acid had a significant increase in their lumbar spine, femoral neck, trochanter, and total hip BMD measurements over the 12-month period. Patients in the control group did not have any significant change in BMD measurements. There was a significant change in the levels of OC and BAP over the 12-month follow-up period. There was also a significant decrease in the number of painful sites experienced by the patients. Treatment of thalassemic osteoporotic patients with zoledronic acid is very effective in increasing BMD at the lumbar spine and hip and in reducing pain; it is also well-tolerated.     

Secondary Osteoporosis in Liver Transplant Recipients: a Longitudinal Study in Patients With and Without Cholestatic Liver Disease

Background: Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation. Methods: A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A—chronic cholestatic liver disease (n = 28), and group B—chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-l-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals. Results: BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving'cyclosporin A. Conclusion: Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.     

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine

OBJECTIVE The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN A prospective study over 2 years of postmenopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS Sixty-four postmenopausal women, ages 47 to 74 (61 ±9, mean ± SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n =23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n =23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = ?0.41 P < 0.001, r = ?0.29 P =0.01 and r = ?0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P >0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P =0.0021, 0.034, 0.0017, 0.011 and >0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P <0.05). CONCLUSIONS In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.     

Renal Sympathetic Denervation in Patients With Hypertension and Chronic Kidney Disease: Does Improvement in Renal Function Follow Blood Pressure Control?

Twenty‐seven patients with resistant hypertension and chronic kidney disease were treated by renal sympathetic denervation (RSD) and followed for 12 months. Patients were retrospectively divided into controlled and uncontrolled blood pressure (BP) groups. Increases in mean estimated glomerular filtration rate (eGFR) were found at months 1, 3, 6, and 12 in the controlled group (P<.0001, for every time point). The mean change in eGFR after 12 months was 18.54±8.15 mL/min/1.73m² higher in the controlled group (P=.0318). In patients in the controlled group with baseline eGFR <45 mL/min/1.73 m², responders (with an increase in eGFR >6.2%) corresponded to 50% at 6 months and 83% at 12 months. In the patients with baseline eGFR ≥45 mL/min/1.73 m², all patients were labeled as responders at months 6 and 12. Median albumin:creatinine ratio after 12 months was lower than baseline only in the controlled group (P=.0003). Our results suggest that patients with this profile who reached BP control by RSD also experienced a significant improvement in renal function.     

Visit-to-visit variability and seasonal variation in blood pressure: Combination of Antihypertensive Therapy in the Elderly,Multicenter Investigation (CAMUI) Trial subanalysis

Abstract

Background: Combination antihypertensive therapy with an angiotensin receptor blocker (ARB) and a calcium channel blocker (CCB) or diuretics is common. This subanalysis investigated blood pressure (BP) variability in patients receiving ARB-based combination therapy. Methods: In a prospective, randomized, open-label trial, hypertensive outpatients (≥65 years) who did not achieve their target BP with ARB monotherapy switched to losartan 50?mg/hydrochlorothiazide 12.5?mg (ARB?+?D) or ARB plus amlodipine 5?mg (ARB?+?C) for 12 months. Clinic BP and heart rate (HR), measured every 3 months, visit-to-visit variability and seasonal variation were evaluated. Results: No significant between-group differences in average, maximum, or minimum systolic or diastolic BP, or HR, were found. Visit-to-visit BP variability (systolic) was significantly higher in the ARB?+?D group than in the ARB?+?C group. When each group was subdivided into two seasonal groups (summer and winter), no significant between-group differences in BP were found. Multivariate regression analyses showed a tendency toward negative correlation between outdoor temperature and urinary albumin:creatinine ratio and estimated glomerular filtration rate at 12 months in the ARB?+?D group. Conclusion: Combination therapy with an ARB plus a CCB may be preferable to that with an ARB plus diuretics for decreasing BP variability. As for seasonal variability, both treatments can be used safely regardless of season.     

Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 μg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm² (2.33%) and 0.021 g/cm² (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm² (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.     

A European multi‐center trial investigating the anti‐restenotic effect of intravascular sonotherapy after stenting of de novo lesions (EUROSPAH: EUROpean Sonotherapy Prevention of Arterial Hyperplasia)

BACKGROUND: Intravascular sonotherapy (IST) reduces neointimal hyperplasia post‐stenting in animal studies. Euro‐SPAH is a multi‐center, double blind, randomized trial investigating the efficacy of IST to reduce in‐stent late loss.

METHODS: Patients with angina or silent ischaemia with stented de novo lesions were randomised to sham or IST. The sample size had a 90% power to detect a late loss difference of 0.21?mm at 6 months. The secondary endpoints were MACE at 1, 6, 12 months and neo‐intimal hyperplasia on IVUS at 6 months.

RESULTS: At 23 sites in Europe, 403 patients were randomized, with successful treatment with sham or IST in 95.6%. There were no significant differences between the groups in terms of baseline demographics or lesion characteristics. Angiographic follow‐up was obtained in 89%. In‐stent late loss was not significantly different. The restenosis rate at 6 months was 23% in the IST group versus 25% in the sham group. The IVUS measurements confirm the absence of effect of IST on neointimal hyperplasia. At one year, the event‐free survival did not significantly differ between the two groups.

CONCLUSION: The use of sonotherapy following stent implantation in de novo lesions does not reduce intra‐stent neointimal hyperplasia, or effect the angiographic restenosis rate compared to sham treatment. (Int J Cardiovasc Intervent 2004; 2:?53–60)     

Comparison of the effects of alendronate and risedronate on bone mineral density and bone turnover markers in postmenopausal osteoporosis

The aim of the study was to compare the effects of once-weekly alendronate sodium and daily risedronate sodium treatment on bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50 patients were included in this study and randomly classified into two groups. Group I (n=25) received risedronate (5 mg/day) and group II (n=25) received alendronate Na (70 mg/week). The study duration was limited to 12 months. The efficacy of the treatment was evaluated by BMD measurements at spine and hip at 6th and 12th months of the treatment, as well as by the measurement of bone turnover markers such as serum osteocalcin (OC), bone-specific alkaline phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in 24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD in all regions revealed a significant increase in BMD in both groups compared to baseline values except for spine (L2–L4) in alendronate group at 6th and 12th month and femoral neck in risedronate group at 6th month. However, the difference in percentage increase in BMD measurements was not statistically significant between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and urine DPD were found to be significantly attenuated at 1st month of the treatment period, and continued to be lowered throughout the 3rd, 6th and 12th months (P<0.05). However, there was no statistically-significant difference between both groups of patients (P>0.05). In conclusion, our results suggest that both treatment protocols provide treatment options of similar efficiencyfor postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD and in slowing the bone turnover. Risedronate seems to havea more potent effect in the spinal region than that of alendronate, although this potency was not statistically significant.     

The effect of magnetic therapy and moderate aerobic exercise on osteoporotic patients: A randomized clinical study

Background:Osteoporosis is a frequent musculoskeletal condition with significant complications that would be a global health problem and one of the major causes of mortality and morbidity.Objectives:The current study aimed to ascertain the impact of pulsed magnetic therapy, aerobic exercise, and a combination of both modalities on osteoporotic female patients postthyroidectomy.Methods:Between May 2018 and September 2019, 45 female patients with osteoporosis were included in the randomized clinical study, their age ranged from 40 to 50 years, had thyroidectomy for at least 6 months ago, and had an inactive lifestyle for at least the previous 6 months. Patients were assigned randomly into 3 equal groups. Group A (magnetic therapy group): received routine medical treatment (bisphosphonates, calcium, and vitamin D) in addition to pulsed magnetic therapy on the hip region for 12 weeks (3 sessions/week). Group B (exercise group): received routine medical treatment plus moderate-intensity aerobic exercise for 12 weeks (3 sessions/week). Group C (combined magnetic therapy and exercise therapy group): received routine medical treatment plus pulsed magnetic therapy and moderate-intensity aerobic exercise for 12 weeks (3 sessions/week). The 3 groups were assessed for bone mineral density (BMD) at baseline by dual-energy x-ray absorptiometry and after 12 weeks of treatment.Results:The results showed that within-group analysis a statistically significant increase was reveled (P < .05) for BMD in the 3 studied groups. Comparing the results among the 3 tested groups revealed a significant increase (P < .05) in posttesting mean values of BMD in group (C) compared to group (A) and group (B). No significant statistical difference in BMD means values between the 2 groups (A) and (B) after testing was detected.Conclusion:Combination of both pulsed magnetic therapy and moderate-intensity aerobic exercise showed significant improvement in BMD at the hip region than using any of the 2 modalities alone.     

Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis

Objectives: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis.

Methods: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n?=?49) or traditional bisphosphonates (n?=?49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment.

Results: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate.

Conclusions: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

The effects of continuous positive airway pressure and mandibular advancement therapy on metabolic outcomes of patients with mild obstructive sleep apnea: a randomized controlled study

Background

Moderate and severe obstructive sleep apnea (OSA) have been independently associated with dyslipidemia. The results of metabolic improvement with continuous positive airway pressure (CPAP) have been controversial. Less evidence exists regarding this issue in mild OSA. A current treatment for mild OSA is mandibular advancement device (MAD) therapy, but its effectiveness on the metabolic profile needs to be compared with CPAP. The purpose of this study was to compare MAD vs CPAP vs no treatment on the metabolic profile during 6 and 12 months of follow-up in patients with mild OSA.

Methods

The inclusion criteria were patients with mild OSA, both genders, ages 18 to 65 years, and body mass index (BMI) of < 35 Kg/m². Patients were randomized in 3 groups (CPAP, MAD, and control). The evaluations included physical examination, metabolic profile, and full polysomnography at baseline, 6 months, and 12 months of follow-up.

Results

Seventy-nine patients with mild OSA were randomized in three treatment groups, with mean age (± SD) of 47?±?9 years, 54% men, and AHI 9.5?±?2.9 events/h. MAD and CPAP reduced AHI at 6 and 12 months compared to the control group. MAD adherence was higher than CPAP at 6 and 12 months. Despite lower adherence compared to MAD, CPAP was more effective in reducing total cholesterol over 12 months (baseline 189.3?±?60.2 mg/dl to 173.4?±?74.3 mg/dl) and low-density lipoprotein cholesterol (LDL-c, baseline 112.8?±?54.9 mg/dl to 94.5?±?67.4 mg/dl).

Conclusions

After 1 year of treatment, CPAP was superior to MAD in reducing total cholesterol and LDL-c in patients with mild OSA.

     

Baseline MRI bone erosion predicts the subsequent radiographic progression in early rheumatoid arthritis patients who achieved sustained good clinical response

Objective: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response.

Methods: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of ‘good clinical response’ was a decrement of disease activity score (DAS) 28?≧?1.2 at three months with achievement of DAS28 remission through 6–12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS)?>?0 was defined as ‘radiographic progression’. Predictors of radiographic progression were determined by logistic regression analysis.

Results: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p?=?.032).

Conclusions: Our data suggest that MRI bone erosion predicts poor radiographic outcome of early-stage RA even if it has been successfully treated.     

Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency

OBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS Twenty-two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency. MEASUREMENTS Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD. RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change ?0.009g/cm², P=0.01), forearm Integral BMD (SPA: median change ?0.016g/cm², P=0.03), lumbar spine BMD (DXA: median change ?0.022g/cm²; P=0.003) and femoral neck BMD (DXA: median change ?0.029g/cm², P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change ?0.035 g/cm², P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass.     

Measurement of hand bone mineral density in early rheumatoid arthritis using dual energy X‐ray absorptiometry

Aims: The earliest radiological change in rheumatoid arthritis (RA) is periarticular osteopenia, which occurs prior to the appearance of erosions and clinically apparent deformities. The aim of the study was to measure periarticular bone mineral density (BMD) in the hands of patients with early RA, using dual energy X‐ray absorptiomentry (DEXA) and to correlate this with markers of disease activity and radiological progression. Methods: The study population (n = 50) of patients with RA of < 3 years duration underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine and clinical assessment at baseline, 6 and 12 months. Hand radiographs were performed at baseline and 12 months. Thirty age‐ and sex‐matched controls also underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine. Results: Hand BMD correlated strongly with sex, height, weight and lumbar and femoral neck BMD in both RA subjects and controls. Baseline hand BMD in RA subjects correlated with baseline serum C‐reactive protein (r = ?0.36, P = 0.01) and 12‐month radiographic score (r = 0.36, P = 0.02). There were small non‐significant decreases in hand, femoral neck and lumbar spine BMD over the 12‐month period. Conclusion: Hand BMD measurement using DEXA is a reproducible, well‐tolerated procedure that warrants further investigation as a component of routine assessment in early RA.     

Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method

Abstract

Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups.

Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group).

Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3–6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3–9) months (p?=?.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p?=?.045).

Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.