Preliminary effect and feasibility of physiotherapy with strength training and protein-rich nutritional supplement in combination with anabolic steroids in cross-continuum rehabilitation of patients with hip fracture: protocol for a blinded randomized controlled pilot trial (HIP-SAP1 trial).

BACKGROUND: A 2014 Cochrane review evaluating the effect of anabolic steroids after hip fracture concluded that the quality of the studies was insufficient to draw conclusions on the effects and recommended further high-quality trials in the field. Therefore, the aim of this pilot trial is to determine the preliminary effect and feasibility of a 12-week multimodal intervention consisting of physiotherapy (with strength training), protein-rich nutritional supplement and anabolic steroid on knee-extension muscle strength and function 14 weeks after hip fracture surgery. METHODS: We plan to conduct a randomized, placebo-controlled pilot trial with 48 patients operated for acute hip fracture. The patients are randomized (1:1) to either (1) physiotherapy with protein-rich nutritional supplement plus anabolic steroid or (2) physiotherapy with protein-rich nutritional supplement plus placebo. Outcome assessments will be carried out blinded at baseline (3-10 days after surgery) and at 14 weeks after entering the trial. Primary outcome is the change from baseline to follow-up in maximal isometric knee-extension muscle strength in the fractured limb. Secondary outcomes are physical performance test, patient-reported outcomes, and measures of body composition. DISCUSSION: If the trial is found feasible and the results show an indication of anabolic steroid being a relevant addition to further enhance the recovery of muscle strength and function in an enhanced recovery after surgery program, this trial will constitute the basis of a larger confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03545347. Preregistered on 4 June 2018.

Time trends in osteoporosis risk factor profiles: a comparative analysis of risk factors, comorbidities, and medications over twelve years.

The aim of this article was to identify prevalent osteoporosis risk factors, medications and comorbidities associated with bone mineral density (BMD). Furthermore to evaluate changes in risk factor profiles over 12 years. 6285 women consecutively referred to an osteoporosis specialist clinic were included. Information of potential risk factors was obtained by questionnaire and clinical examination. Additional information on medication use, comorbidities and fractures were obtained from national registries. An association (<0.05) between well-known risk factors negatively influencing bone health was established in a real-life setting. The prevalence of osteoporosis and proportion of patient's having comorbidity's associated with osteoporosis were increasing during the inclusion period (start 23.8 %, end 29.7 %). Increasing age (OR = 1.05), current smoking (OR = 1.18), estrogen deficiency (OR = 1.7), hyperthyroidism (OR = 1.5), previous major osteoporotic fracture (OR = 1.7), former osteoporosis treatment (OR = 3.5), higher BMI (OR = 0.87), use of calcium supplementation (OR = 1.2), high exercise level (OR = 0.7), and use of thiazide diuretics (OR = 0.7) were identified as predictors of osteoporosis by DXA. Rheumatoid arthritis (OR = 2.4) and chronic pulmonary disease (OR = 1.5) was associated with site-specific osteoporosis by DXA at the total hip. Current use of loop diuretics (OR = 1.7) and glucocorticoid use (OR = 1.04-1.06) were associated with both total hip and femoral neck T-score <-2.5. Our data confirms an independent negative association with BMD of many established risk factors, certain comorbidities, and medications. Exercise level, use of loop diuretics, and prevalent chronic pulmonary disease, risk factors not included in fracture risk calculators were associated with osteoporosis by DXA. Time trends indicate risk profile is dynamic, with increasing focus on secondary osteoporosis.

Nutritional intake and status in persons with alcohol dependency: data from an outpatient treatment programme.

PURPOSE: Malnutrition increases the risk of developing alcohol-related complications. The aim of this study was to describe nutrient intake, nutritional status and nutrition-related complications in a Danish population of outpatients with alcohol dependency. METHODS: This was a cross-sectional study with a 6-month follow-up enrolling persons with alcohol dependency (n = 80) admitted to a hospital-based outpatient clinic. Body mass index, the waist-to-hip ratio and handgrip strength (HGS) were measured, a 7-day food diary was collected, and biochemical testing was conducted. Dual-energy X-ray absorptiometry was performed to determine body composition and bone mineral density (BMD). RESULTS: In total, 64% of the patients with alcohol dependency had vitamin D insufficiency (25-OH-vit D <50 nmol/l). Compared with surveys of the general population, the patients with alcohol dependency had lower energy intake (p = 0.008), s-zinc levels (p < 0.001), s-magnesium levels (p = 0.02), Z-scores for BMD (lumbar spine, p = 0.03; total hip, p = 0.009) and HGS (p < 0.001). Osteopenia was observed in 52% of individuals, and overt osteoporosis was noted in 7%. Comparing baseline data with data from the follow-up (n = 30), we found a decrease in s-CRP (p = 0.002) and s-alanine amino transferase (p = 0.01) levels and an increase in s-parathyroid hormone levels (p = 0.02). CONCLUSIONS: Patients with alcohol dependency have an altered nutritional status and risk of complications, as evidenced by osteopenia/osteoporosis and reduced muscle strength. Treatment at an outpatient clinic improved the variables related to liver function, but no change was observed in nutritional status over time. These findings suggest that specific screening and targeted treatment regimens for nutritional deficits could be beneficial.

The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males: results of a clinical trial.

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 µg calcitriol and 1,200 IU (30 µg) cholecalciferol, 17 participants to (B) 1,200 IU cholecalciferol, and 15 participants to (C) placebo. At baseline and after 16 weeks, we determined collagen type 1 trimeric cross-linked peptide (CTx), procollagen type 1 N-terminal peptide (P1NP), parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. We determined naive CD4(+) and CD8(+), activated CD4(+) and CD8(+), and regulatory CD4(+)CD25(+)CD127(low) T lymphocytes. Baseline levels of P1NP and CTx correlated (coefficient 0.5, p<0.001) with each other but not with PTH, 25OHD, or 1,25(OH)2D. In patients receiving calcitriol and cholecalciferol, the mean levels of P1NP (p<0.001) and CTx (p= 0.002) declined significantly compared to our placebo group. Based on changes in P1NP and CTx, we estimated that net bone formation occurred more frequently in group A compared to groups B and C. PTH correlated inversely with naive CD4(+) and CD8(+) cells. Otherwise, no relationships between bone markers and T lymphocytes were demonstrated. Supplementation with calcitriol and cholecalciferol induced biochemical indications of bone formation in HIV-1 patients.

Changes in 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D are associated with maturation of regulatory T lymphocytes in patients with chronic pancreatitis: a randomized controlled trial.

OBJECTIVES: We studied the impact of changes in 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) on regulatory T lymphocytes (Tregs) in patients with chronic pancreatitis (CP) and fat malabsorption in a prospective clinical trial. METHODS: The patients were randomized to 1 of 3 treatments during 10 weeks: weekly UV-B in a tanning bed (group A), 1520-IU/d vitamin D supplement (group B), or placebo (group C). A placebo tanning bed was used in groups B and C. We determined the levels of CD4 Tregs (CD3(+)CD4(+)CD25(+)CD127(low)FoxP3(+)) and CD8(+) Tregs (CD3(+)CD8(+)CD25(+)CD127(low)FoxP3(+)), together with 25OHD and 1,25(OH)2D. For baseline comparisons, we included 8 healthy individuals. Of the 30 included patients, 27 (group A, 7 patients; group B, 9 patients; and group C, 11 patients) completed the protocol. RESULTS: The baseline levels of CD4(+) Tregs relative to total CD4(+) count were higher in 22 patients with CP compared with healthy controls (2.8% vs 1.9%, P < 0.05) and were comparable for CD8+ Tregs (0.13% vs 0.05%, P = 0.3). Increases in levels of CD4(+) Tregs correlated to changes in 1,25(OH)(2)D (2% per 100 pmol/L, P = 0.002) and 25OHD (3% per 100 nmol/L, P = 0.01). CONCLUSIONS: Patients with CP have elevated relative levels of CD4(+) Tregs. Increases in 25OHD and 1,25(OH)(2)D were both related with increases in levels of Tregs.

Correlation of increases in 1,25-dihydroxyvitamin D during vitamin D therapy with activation of CD4+ T lymphocytes in HIV-1-infected males.

BACKGROUND: In HIV-1-infected individuals, levels of CD4+ T lymphocytes are depleted and regulatory T-lymphocytes (Tregs) are elevated. In vitro studies have demonstrated effects of vitamin D on the growth and differentiation of these cells. We speculated whether supplementation with vitamin D could have an effect on CD4+ T lymphocytes or Tregs in HIV-1-infected males. METHODS: We conducted a placebo-controlled randomized study that ran for 16 weeks and included 61 HIV-1-infected males, of whom 51 completed the protocol. The participants were randomized to 1 of 3 daily treatments: (1) 0.5-1.0 µg calcitriol and 1200 IU (30 µg) cholecalciferol, (2) 1200 IU cholecalciferol, (3) placebo. Percentages of the following T-lymphocyte subsets were determined: naïve CD4+ and CD8+ cells, activated CD4+ and CD8+ cells, and CD3+CD4+CD25+CD127low Tregs. Furthermore 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone were measured. RESULTS: No significant changes of the studied T-lymphocyte subsets occurred in the treatment groups compared to the placebo group. Increases in 1,25-dihydroxyvitamin D were associated with increases in activated CD4+ T lymphocytes (P = .001) and Tregs (P = .01) in adjusted models. Changes in parathyroid hormone correlated inversely with Tregs (P = .02). Smokers had higher levels of naïve CD4+ T lymphocytes (37% vs 25%;P = .01), naïve CD8+ T lymphocytes (28% vs 19%; P = .03), and Tregs (9% vs 7%; P = .03). CONCLUSION: Cholecalciferol and calcitriol administered during 16 weeks did not change the levels of T-lymphocyte fractions compared to placebo. However, increases in 1,25-dihydroxyvitamin D were associated with an expansion of activated CD4+ cells and Tregs.

The combination of structural parameters and areal bone mineral density improves relation to proximal femur strength: an in vitro study with high-resolution peripheral quantitative computed tomography.

The aim of this study was to assess structural indices from high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the human proximal femur along with areal bone mineral density (aBMD) and compare the relationship of these parameters to bone strength in vitro. Thirty-one human proximal femur specimens (8 men and 23 women, median age 74 years, range 50-89) were examined with HR-pQCT at four regions of interest (femoral head, neck, major and minor trochanter) with 82 µm and in a subgroup (n = 17) with 41 µm resolution. Separate analyses of cortical and trabecular geometry, volumetric BMD (vBMD), and microarchitectural parameters were obtained. In addition, aBMD by dual-energy X-ray absorptiometry (DXA) was performed at conventional hip regions and maximal compressive strength (MCS) was determined in a side-impact biomechanical test. Twelve cervical and 19 trochanteric fractures were confirmed. Geometry, vBMD, microarchitecture, and aBMD correlated significantly with MCS, with Spearman's correlation coefficients up to 0.77, 0.89, 0.90, and 0.85 (P < 0.001), respectively. No differences in these correlations were found using 41 µm compared to 82 µm resolution. In multiple regression analysis of MCS, a combined model (age- and sex-adjusted) with aBMD and structural parameters significantly increased R (2) values (up to 0.90) compared to a model holding aBMD alone (R (2) up to 0.78) (P < 0.05). Structural parameters and aBMD are equally related to MCS, and both cortical and trabecular structural parameters obtained from HR-pQCT images hold information on bone strength complementary to that of aBMD.

Patients with Rett syndrome sustain low-energy fractures.

We present the first case-control study addressing both fracture occurrence and fracture mechanisms in Rett syndrome (RTT). Two previous studies have shown increased fracture risk in RTT. This was also our hypothesis regarding the Danish RTT population. Therefore, we investigated risk factors associated with low-energy trauma and the association to methyl-CpG-binding protein 2 (MECP2) mutations. A total of 61 female patients with RTT and 122 healthy controls matched according to age and pubertal/menopause status were examined by questionnaires, bone biochemical markers in blood, and clinical and x-ray evaluations. National register search on fracture diagnoses was done to obtain complete fracture histories. Our results showed that patients with RTT sustained significantly more low-energy fractures from early age compared with controls, even though overall fracture occurrence apparently was not increased. Low-energy fractures were significantly associated with less mobility and lack of ambulation. Associations with MECP2 mutations or epilepsy were not demonstrated, contrary to previous findings. Blood biochemistry indicated a possible need for D vitamin supplementation in RTT. Our study casts light on fracture occurrence in RTT and points to a need for future research in bone development and fracture risk to establish directions for improved prevention and treatment of low-energy fractures in RTT.