The effects of postprandial exercise and meal glycemic index on plasma glucose and glucoregulatory hormone responses after Roux-en-Y gastric bypass.

Postprandial hypoglycemia is a complication of Roux-en-Y gastric bypass (RYGB), but the effects of postprandial exercise and meal glycemic index (GI) on postprandial glucose and glucoregulatory hormone responses are unknown. Ten RYGB-operated and 10 age and weight-matched unoperated women completed four test days in random order ingesting mixed meals with high GI (HGI, GI = 93) or low GI (LGI, GI = 54), but matched on energy and macronutrient content. Ten minutes after meal completion, participants rested or cycled for 30 min at 70% of maximum oxygen uptake (V̇o2max). Blood was collected for 4 h. Postprandial exercise did not lower plasma nadir glucose in RYGB after HGI (HGI/rest 3.7 ± 0.5 vs. HGI/Ex 4.1 ± 0.4 mmol/L, P = 0.070). Replacing HGI with LGI meals raised glucose nadir in RYGB (LGI/rest 4.1 ± 0.5 mmol/L, P = 0.034) and reduced glucose excursions (Δpeak-nadir) but less so in RYGB (-14% [95% CI: -27; -1]) compared with controls (-33% [-51; -14]). Insulin responses mirrored glucose concentrations. Glucagon-like peptide 1 (GLP-1) responses were greater in RYGB versus controls, and higher with HGI versus LGI. Glucose-dependent insulinotropic polypeptide (GIP) responses were greater after HGI versus LGI in both groups. Postexercise glucagon responses were lower in RYGB than controls, and noradrenaline responses tended to be lower in RYGB, whereas adrenaline responses were similar between groups. In conclusion, moderate intensity cycling shortly after meal intake did not increase the risk of postprandial hypoglycemia after RYGB. The low GI meal increased nadir glucose and reduced glucose excursions compared with the high GI meal. RYGB participants had lower postexercise glucagon responses compared with controls.NEW & NOTEWORTHY We investigate the effect of moderate exercise after a high or a low glycemic index meal on nadir glucose and glucoregulatory hormones in gastric bypass-operated individuals and in matched unoperated controls. Cycling shortly after meal intake did not increase the risk of hypoglycemia in operated individuals. The low glycemic index meal increased glucose nadir and reduced excursions compared with the high glycemic index meal. Operated individuals had lower postexercise glucagon responses compared with controls.

Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake.

BACKGROUND/OBJECTIVES: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure. SUBJECTS/METHODS: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting. RESULTS: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]). CONCLUSIONS: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study.

Hypophosphatasia (HPP) is a rare disease affecting bone mineralization. Adults with HPP have an increased occurrence of low-energy fractures, which cannot be explained by reduced bone mass assessed by dual energy X-ray absorptiometry. The bone phenotype in adults with HPP requires further studies investigating bone strength and bone structural parameters. INTRODUCTION: Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism, characterized by broad-ranging clinical manifestations and severity. However, studies investigating the clinical spectrum in adults with HPP compared to a control group are scarce. The aim of this study was to evaluate biochemical and clinical characteristics as well as bone health in a Danish cohort of adults with HPP. METHODS: We conducted a cross-sectional study assessing biochemical parameters, fracture prevalence, bone mineral density (BMD), bone turnover markers, physical performance and pain characteristics in 40 adults with HPP and 40 sex-, age-, BMI- and menopausal status-matched healthy controls. RESULTS: Patients with HPP had a significantly higher prevalence of non-vertebral, low-energy fractures (p = < 0.001). BMD at the lumbar spine, total hip, femoral neck, forearm and whole body did not differ between the groups. Low levels of the bone-specific alkaline phosphatase correlated significantly with higher BMD at the lumbar spine and femoral neck in both groups. The bone formation marker N-terminal propeptide of type 1 procollagen was significantly lower in patients with HPP than healthy controls (p = 0.006). Adults with HPP had significantly reduced walking capability (p = < 0.001) and lower body strength (p = < 0.001). Chronic pain was significantly more prevalent in adults with HPP than the control group (p = 0.029). CONCLUSIONS: The increased occurrence of low-energy fractures in adults with HPP is not explained by low BMD. Adults with HPP have reduced physical performance when compared with healthy controls.

Frailty and osteoporosis in patients with hip fractures under the age of 60-a prospective cohort of 218 individuals.

Research on younger patients with hip fractures is limited. This study adds knowledge on patient and injury characteristics, and DXA was investigated at the time of the fracture. Risk factors for osteoporosis and fractures were numerous among young patients, and osteoporosis was markedly more prevalent than in the general population. INTRODUCTION: Knowledge on younger patients with hip fractures is limited. Common preconceptions are that they suffer fractures due to high-energy trauma, alcohol or substance use disorder but not associated to osteoporosis. We aimed to descriptively analyze the characteristics of young and middle-aged patients with hip fractures and examine bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) at the time of the fracture. METHODS: A prospective multicenter cohort study on adult patients with hip fractures below age 60 collected detailed information on patient characteristics regarding demographics, trauma mechanism, previous fractures, comorbidity and medication, and lifestyle factors. DXA results were compared to population-based reference data. RESULTS: The cohort contains 91 women and 127 men, median age 53 (IQR 47-57). Most fractures, 83%, occurred in patients aged 45-59. Two-thirds of all fractures resulted from low-energy trauma. Half of the patients had prior fractures after age 20. Thirty-four percent were healthy, 31% had one previous disease, and 35% had multiple comorbidities. Use of medication associated with increased fracture risk was 32%. Smoking was prevalent in 42%, harmful alcohol use reported by 29%, and signs of drug-related problems by 8%. Osteoporosis according to WHO criteria was found in 31%, osteopenia in 57%, and normal BMD in 12%. CONCLUSION: In patients with hip fractures below age 60, risk factors for osteoporosis and fractures were numerous. Moreover, the prevalence of osteoporosis was markedly higher than in the general population. We suggest that young and middle-aged patients with hip fractures undergo a thorough health investigation including DXA, regardless of trauma mechanism.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Feasibility and preliminary effect of anabolic steroids in addition to strength training and nutritional supplement in rehabilitation of patients with hip fracture: a randomized controlled pilot trial (HIP-SAP1 trial).

BACKGROUND: Anabolic steroid has been suggested as a supplement during hip fracture rehabilitation and a Cochrane Review recommended further trials. The aim was to determine feasibility and preliminary effect of a 12-week intervention consisting of anabolic steroid in addition to physiotherapy and nutritional supplement on knee-extension strength and function after hip fracture surgery. METHODS: Patients were randomized (1:1) during acute care to: 1. Anabolic steroid (Nandrolone Decanoate) or 2. Placebo (Saline). Both groups received identical physiotherapy (with strength training) and a nutritional supplement. Primary outcome was change in maximal isometric knee-extension strength from the week after surgery to 14 weeks. Secondary outcomes were physical performance, patient reported outcomes and body composition. RESULTS: Seven hundred seventeen patients were screened, and 23 randomised (mean age 73.4 years, 78% women). Target sample size was 48. Main limitations for inclusion were "not home-dwelling" (18%) and "cognitive dysfunction" (16%). Among eligible patients, the main reason for declining participation was "Overwhelmed and stressed by situation" (37%). Adherence to interventions was: Anabolic steroid 87%, exercise 91% and nutrition 61%. Addition of anabolic steroid showed a non-significant between-group difference in knee-extension strength in the fractured leg of 0.11 (95%CI -0.25;0.48) Nm/kg in favor of the anabolic group. Correspondingly, a non-significant between-group difference of 0.16 (95%CI -0.05;0.36) Nm/Kg was seen for the non-fractured leg. No significant between-group differences were identified for the secondary outcomes. Eighteen adverse reactions were identified (anabolic = 10, control = 8). CONCLUSIONS: Early inclusion after hip fracture surgery to this trial seemed non-feasible, primarily due to slow recruitment. Although inconclusive, positive tendencies were seen for the addition of anabolic steroid. TRIAL REGISTRATION: Clinicaltrials.gov NCT03545347 .

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia.

Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor.

It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both mineral apposition rate and thickness of the endocortical osteoid layer were higher in the P2Y2R-Tg rats. µCT analysis showed reduced trabecular thickness and structural model index in P2Y2R-Tg rats. Femoral length was increased in the P2Y2R-Tg rats compared to Wt rats. In vitro, there was an increased formation of osteoclasts, but no change in total resorption in cultures from P2Y2R-Tg rats. The formation of mineralized nodules was significantly reduced in the osteoblastic cultures from P2Y2R-Tg rats. In conclusion, our study suggests that P2Y2R is involved in regulation of bone turnover, due to the effects on both osteoblasts and osteoclasts and that these effects might be relevant in the regulation of bone growth.

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.

Atypical femoral fracture in an osteogenesis imperfecta patient successfully treated with teriparatide.

OBJECTIVE: We report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described. METHODS: This is a case report of an AFF treated with teriparatide. RESULTS: The patient was treated with hormone replacement therapy for 18 years and bisphosphonates for 9 years before suffering a spontaneous AFF in the form of a dislocated noncomminute transverse fracture of the right femoral shaft, and an open reduction and internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and another fracture distal to the nail, the patient was reoperated on with exchange ORIF and off-label treatment with teriparatide 20 µg/day was started. An X-ray 1 month later showed early signs of fracture healing. A subsequent X-ray 6 months after the last operation showed a solid healing of both right femoral fractures. CONCLUSION: This is a rare case that highly suggests a potential fracture healing effect of teriparatide treatment and highlights a potential significant practical therapeutic consideration in relation to the management of AFF with delayed healing.

Cancer risk in patients treated with denosumab compared with alendronate: A population-based cohort study.

BACKGROUND: Antiresorptive treatment is currently used in millions of patients with osteoporosis and cancer worldwide. Early studies of denosumab suggested a small signal in ovarian cancer incidence and emerging data suggest that denosumab stimulates germ cell proliferation in the gonads. This study aims to determine the association between the use of denosumab and the risk of reproductive cancers compared with the use of alendronate. RESEARCH DESIGN AND METHODS: Using a cohort study design, we used the Danish nationwide registries to identify a population of subjects ≥50 years of age during 2010-2017 who started denosumab after being on alendronate treatment for at least six months. The cohort was matched 1:2 with patients who had been treated with alendronate alone for at least six months. The risk of reproductive cancers and the risk difference between groups were estimated using the Longitudinal Targeted Maximum Likelihood Estimation (L-TMLE) method. RESULTS: We identified 6054 Danish individuals who underwent treatment with denosumab. These individuals were matched with 12,108 receiving alendronate. The absolute risk of reproductive cancer was 1.05 % (95 % CI 0.75-1.34) after three years for denosumab users and was not different 0.03 % (-0.34-0.39) than for alendronate users. In supplemental analyses, there was no increased risk of non-reproductive cancers associated with the use of denosumab (risk difference of 0.54 % (-0.41-1.19). Analysis comparing denosumab users with the general population gave similar results. CONCLUSION: There was no difference in the risk of cancer following treatment with denosumab compared to treatment with alendronate assessed after a short follow-up of 3 years.

Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial.

Importance: A major concern with weight loss is concomitant bone loss. Exercise and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent weight loss strategies that may protect bone mass despite weight loss. Objective: To investigate bone health at clinically relevant sites (hip, spine, and forearm) after diet-induced weight loss followed by a 1-year intervention with exercise, liraglutide, or both combined. Design, Setting, and Participants: This study was a predefined secondary analysis of a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. Eligible participants included adults aged 18 to 65 years with obesity (body mass index of 32-43) and without diabetes. Data analysis was conducted from March to April 2023, with additional analysis in February 2024 during revision. Interventions: After an 8-week low-calorie diet (800 kcal/day), participants were randomized to 1 of 4 groups for 52 weeks: a moderate- to vigorous-intensity exercise program (exercise alone), 3.0 mg daily of the GLP-1 RA liraglutide (liraglutide alone), the combination, or placebo. Main Outcomes and Measures: The primary outcome was change in site-specific bone mineral density (BMD) at the hip, lumbar spine, and distal forearm from before the low-calorie diet to the end of treatment, measured by dual-energy x-ray absorptiometry in the intention-to-treat population. Results: In total, 195 participants (mean [SD] age, 42.84 [11.87] years; 124 female [64%] and 71 male [36%]; mean [SD] BMI, 37.00 [2.92]) were randomized, with 48 participants in the exercise group, 49 participants in the liraglutide group, 49 participants in the combination group, and 49 participants in the placebo group. The total estimated mean change in weight losses during the study was 7.03 kg (95% CI, 4.25-9.80 kg) in the placebo group, 11.19 kg (95% CI, 8.40-13.99 kg) in the exercise group, 13.74 kg (95% CI, 11.04-16.44 kg) in the liraglutide group, and 16.88 kg (95% CI, 14.23-19.54 kg) in the combination group. In the combination group, BMD was unchanged compared with the placebo group at the hip (mean change, -0.006 g/cm2; 95% CI, -0.017 to 0.004 g/cm2; P = .24) and lumbar spine (-0.010 g/cm2; 95% CI, -0.025 to 0.005 g/cm2; P = .20). Compared with the exercise group, BMD decreased for the liraglutide group at the hip (mean change, -0.013 g/cm2; 95% CI, -0.024 to -0.001 g/cm2; P = .03) and spine (mean change, -0.016 g/cm2; 95% CI, -0.032 to -0.001 g/cm2; P = .04). Conclusions and Relevance: In this randomized clinical trial, the combination of exercise and GLP-1RA (liraglutide) was the most effective weight loss strategy while preserving bone health. Liraglutide treatment alone reduced BMD at clinically relevant sites more than exercise alone despite similar weight loss. Trial Registration: EudraCT: 2015-005585-32.

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.

Transient osteoporosis of the hip.

Transient osteoporosis of the hip (TOH) is a rare condition with acute onset of hip pain. TOH is self-limiting and often leads to complete remission of symptoms within 6-12 months. This case report presents a 44-year-old male diagnosed with TOH. As part of the treatment plan, the patient received intravenous bisphosphonate with 5 mg zoledronic acid. A few weeks after administration, the patient reported almost full symptomatic remission.

Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation.

BACKGROUND: Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP. METHODS: In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system. RESULTS: Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p = 0.041). CONCLUSIONS: BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP.

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.

Variations in serum 25-hydroxyvitamin D during acute pancreatitis: an exploratory longitudinal study.

OBJECTIVES: We tested the hypothesis that 25-hydroxyvitamin D3 (25OHD) changes during acute inflammation in humans. METHODS: Patients with first episode of acute pancreatitis were included. Blood samples were acquired on admission and on days 1, 2, and 14. RESULTS: In total, 73 patients (35 males, median age 59) entered the study. On admission, the distribution of 25-OHD levels was as follows: severely deficient (<13 nmol/L) 23%; deficient (13-25 nmol/L) 20%; insufficient (26-50 nmol/L) 40%; and normal (<50 nmol/L) 17%. There was a significant fall and linear trend in 25OHD, albumin, and hemoglobin from day 0 to day 2. From day 0 to day 2 the drop in 25OHD was 3.1 nmol/L (95% CI 0.59-5.63). The changes from day 0 to day 2 in 25OHD were associated with changes in C-reactive protein (p = 0.02) but not with leukocyte or monocyte count. CONCLUSIONS: The 25OHD levels dropped during the first 2 days of acute pancreatitis beyond what was expected based on 25OHD half-life. This study supports our hypothesis that an acute inflammatory condition utilizes 25OHD, but other mechanisms could interfere.

Severe hypocalcemia due to hypoparathyroidism associated with HIV: A case report.

Calcemia is not routinely determined among people living with human immunodeficiency virus (HIV). In people living with HIV, the most frequent electrolyte disturbance is hyponatremia and since symptoms of hypocalcemia often are unspecific, calcium is typically measured with some delay. Hypocalcemia in people living with HIV is mainly due to indirect causes such as vitamin D deficiency, renal failure, or drug related. However, in rare cases direct viral involvement of the parathyroid glands has been reported. We present a case of a 67-year-old male living with HIV who presented at an emergency department with symptomatic severe hypocalcemia, without any previous history of neck surgery, radiation therapy or large infections in the head and neck area. At the time of admission serum concentrations were for ionized calcium 0.98 mmol/L (ref. 1.18-1.32 mmol/L) and PTH 1.3 mmol/L (ref. 2.0-8.5 pmol/L). Vitamin D status was sufficient with 25OHD at 73 nmol/L to 112 nmol/L (ref. 60-160 nmol/L) from 2016 through 2019. The patient was diagnosed with primary hypoparathyroidism and was treated with Alphacalcidol 0,5 µg × 1/daily, calcium 500 mg × 4 the first day followed by 400 mg × 2 and magnesium 360 mg × 3, which induced rapid clinical recovery with dissolvement of muscular pain and biochemical improvement. This case study suggests that further studies are needed to investigate the added value of routine monitoring for hypocalcemia as part of clinical follow-up of people living with HIV.

Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study.

The aim of this descriptive cross-sectional study was to describe the prevalence of hypovitaminosis D in a cohort of HIV-seropositive males. Blood samples were collected in November and December 2004 and analyzed in the hospital laboratory. The concentration of 25-hydroxyvitamin D (25(OH)D) was defined as excellent when >75 nmol/l, normal when >50 nmol/l, insufficient when <50 nmol/l, deficient when <25 nmol/l and severely deficient when <12.5 nmol/l. Patient information was extracted from the medical records. A total of 115 males, median age 44 y (range 19-63 y), were included in the study. The median 25(OH)D concentration was 43.0 nmol/l (range 8-163 nmol/l) and the 25(OH)D level was excellent in 13%, normal in 27%, insufficient in 36%, deficient in 20%, and severely deficient in 4% of the cases. Vitamin D level was not associated with age, y with HIV infection, highly active antiretroviral therapy (HAART) or CD4 count. Compared to patients not in treatment, patients on HAART (n = 71) had higher levels of total alkaline phosphatase (median 83.0 vs 75.5 U/l; p = 0.031) and lower, though not significantly, total body mineral density (1.055 vs 1.107 g/cm(2); p = 0.077). This study confirms that the prevalence of hypovitaminosis is high among HIV-infected patients.