Background:
Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs).
...Objectives:
The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS.
Methods:
A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD.
Results:
Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD.
Conclusion:
Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients.
Summary
Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured ...with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment.
Introduction
In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting.
Methods
In this registry-based cohort study of osteoporosis patients (
n
= 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women.
Results
Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (
p
= 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (
p
= 0.03), femoral neck (
p
= 0.04), and lumbar spine (
p
= 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (
p
= 0.02) and lumbar spine (
p
= 0.006).
Conclusion
Measurement of pre-treatment BTM levels predicts osteoporosis patients’ response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.
Background
Multiple sclerosis (MS) patients are at increased risk of reduced bone mineral density (BMD) and fractures. The aetiology of bone loss in MS is unclear. Trabecular bone score (TBS) is a ...novel analytical tool that provides a measurement of the bone microarchitecture. Decreased TBS predicts increased fracture risk independently of BMD. To date, no studies have investigated TBS in MS patients.
Objectives
To assess bone quality in MS patients by TBS and to evaluate potential risk factors that may affect BMD and TBS in patients with MS.
Methods
Two hundred sixty MS patients were included. TBS was calculated using TBS iNsight software (MediMaps®). Multivariable regression analyses were performed with information on smoking, alcohol, glucocorticoid (GC) treatment, sun exposure, physical activity, vitamin D and BMI.
Results
Trabecular bone score was not significantly different from an age‐matched reference population. Low TBS was associated with high age (P = .014) and smoking (P = .03). Smoking and physical inactivity were associated with low BMD in spine (P = .034, P = .032). GC treatment was not associated with TBS.
Conclusion
We could not find altered TBS values among MS patients, suggesting that BMD alone, and not the bone microarchitecture, is affected in MS. However, larger studies are needed to verify these findings and to establish the role of TBS in MS. As in the background population, physical activity and non‐smoking habits are associated with better bone health in MS.
Twenty to thirty percent of testicular cancer (TC) survivors have elevated serum levels of luteinising hormone (LH) with or without corresponding low testosterone levels (Leydig cell dysfunction) ...during clinical follow-up for TC. However, it remains to be clarified if this subgroup of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up.
TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig cell function during follow-up were eligible for participation in the study. Markers of systemic inflammation and prevalence of MetS were compared between TC survivors with Leydig cell dysfunction and the control group.
Of 158 included TC survivors, 28 (18%) had uncompensated Leydig cell dysfunction, 59 (37%) had compensated Leydig cell dysfunction and 71 (45%) had normal Leydig cell function during follow-up. MetS and markers of systemic inflammation were evaluated at a median follow-up of 9.7 years (interquartile range 4.1–17.1) after TC treatment. The prevalence of MetS was significantly lower among patients with compensated Leydig cell dysfunction during follow-up (12% versus 27%, p = 0.04), whereas there was no difference between TC survivors with uncompensated Leydig cell dysfunction and controls (33% versus 27%, p = 0.5). Apart from high-sensitivity C-reactive protein which was higher in TC survivors with uncompensated Leydig cell dysfunction during follow-up, there was no evidence of increased systemic inflammation in patients with Leydig cell dysfunction during clinical follow-up. Total testosterone at follow-up was significantly associated with MetS, whereas there was no association between LH and MetS.
We did not find evidence that TC survivors with Leydig cell dysfunction during clinical follow-up had increased long-term risk of MetS. Total testosterone at follow-up was significantly associated with MetS. The study is registered at www.clinicaltrials.govNCT02240966.
•Low serum levels of total testosterone were associated with metabolic syndrome.•Elevated serum levels of luteinising hormone were not associated with metabolic syndrome.•Low total testosterone and elevated luteinising hormone on >1 occasion is suggestive of testosterone deficiency.•Testosterone treatment may reduce the risk of metabolic syndrome in testicular cancer survivors with testosterone deficiency.
Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It ...has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover.
In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX).
After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01-0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01-0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX.
12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.
Retrospective chart review.
To investigate the extent of renal deterioration in patients with spinal cord injury (SCI) and to identify risk indicators associated with renal deterioration.
Clinic for ...Spinal Cord Injuries, Rigshospitalet, Hornbæk, Denmark.
This study included 116 patients admitted to our clinic with a traumatic SCI sustained between 1956 and 1975. Results from renography and (51)Cr-EDTA plasma clearance were collected from medical records from time of injury until 2012, and the occurrence of renal deterioration was analysed by cumulative incidence curves. The impact of demographics, neurological level and completeness of SCI, urinary tract stones, dilatation of the upper urinary tract (UUT) and bladder-emptying methods were analysed with Cox proportional hazard ratios.
The bladder-emptying methods used for the longest period were reflex triggering (63%), bladder expression (22%), indwelling catheter (5%), normal voiding (4%), ileal conduit (3%) and clean intermittent catheterisation (2%). The cumulative risk of moderate renal deterioration (functional distribution outside 40-60% on renography or relative glomerular filtration rate (GFR) ⩽75% of expected according to age and gender) was 58%. The cumulative risk of severe renal deterioration (functional distribution outside 30-70% on renography or relative GFR⩽51%) was 29% after 45 years postinjury. Only dilatation of UUT and renal/ureter stone requiring removal significantly increased the risk of moderate and severe renal deterioration.
Renal deterioration occurs at any time after injury, suggesting that lifelong follow-up examinations of the renal function are important, especially in patients with dilatation of UUT and/or renal/ureter stones.
The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E2 (PGE2) and its possible mechanisms have previously not been systematically studied in ...man. We hypothesized that infusion of PGE2 might induce headache and vasodilation of cranial vessels. PGE2 (0.40 μg kg−1 min−1) or saline was infused for 25 min into 11 healthy subjects in a cross-over, double-blind study. Headache intensity was scored on a verbal rating scale from 0 to 10. In addition, we recorded mean flow in the middle cerebral artery (VMCA) by transcranial Doppler and diameter of the superficial temporal artery (STA) by high-resolution ultrasonography. All 11 subjects reported headache on the PGE2 day and no subjects reported headache on the placebo day (P = 0.001). During the immediate phase (0–30 min) (P = 0.005) and the postinfusion phase (30–90 min) (P = 0.005), the area under the curve for headache score was significantly larger on the PGE2 day compared with the placebo day. PGE2 caused dilatation of the STA (23.5%; 95% CI 14.0, 37.8) and the MCA (8.3%; 95% CI 4.0, 12.6). We suggest that PGE2 induces headache by activation and sensitization of cranial perivascular sensory afferents.
The role of the parasympathetic nervous system in the pathogenesis of migraine is disputed. The headache-eliciting effect of the parasympathetic neurotransmitter, vasoactive intestinal polypeptide ...(VIP), and its effect on cerebral arteries and brain haemodynamics has not been systematically studied in man. We hypothesized that infusion of VIP might induce headache in healthy subjects and cause changes in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9± saline) was infused for 25 min into 12 healthy young volunteers in a crossover, double-blind design. Headache was scored on a verbal rating scale from 0 to 10, regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography and 133Xe inhalation and mean flow velocity in the middle cerebral artery (VmeanMCA) was measured with transcranial Doppler ultrasonography. The headache was very mild with a maximum score of 2 and described as a pressing or throbbing sensation. Five participants developed headache during VIP and one during placebo. During the infusion, a significant drop in VmeanMCA was seen for VIP compared with placebo (P < 0.001), but the effect quickly waned and no difference was found when comparing the time between 30 and 120 min. In addition, no significant difference in the diameter of the MCA could be found during the infusion. No significant differences in rCBF (P = 0.10) were found between VIP and placebo. A marked dilation of the superficial temporal artery was seen (P = 0.04) after VIP in the first 30 min but no difference was found when comparing the time between 30 and 120 min. We found no difference in mean arterial blood pressure between VIP and placebo days but the heart rate increased significantly on a VIP day compared with a placebo day (AUC0–30min, P < 0.001). Plasma VIP was significantly higher on a VIP day compared with placebo (AUC0–80min, P < 0.001). These results show that VIP causes a decrease in VmeanMCA without affecting rCBF. In spite of a marked vasodilator effect in the extracranial vessels and increased plasma VIP, healthy subjects developed only a very mild headache.
Objectives
While renal impairment is reported more frequently in people living with HIV (PLWH) than in the general population, the PLWH samples in previous studies have generally been dominated by ...those at high renal risk.
Methods
Caucasian PLWH who were virologically suppressed on antiretroviral treatment and did not have injecting drug use or hepatitis C were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Sex‐ and age‐matched controls were recruited 1:4 from the Copenhagen General Population Study up to November 2016. We defined renal impairment as one measurement of estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2, and assessed associated factors using adjusted logistic regression models. The impact of HIV‐related factors was explored in a subanalysis.
Results
Among 598 PLWH and 2598 controls, the prevalence of renal impairment was 3.7% 95% confidence interval (CI) 2.3–5.5% and 1.7% (95% CI 1.2–2.2%; P = 0.0014), respectively. After adjustment, HIV status was independently associated with renal impairment odds ratio (OR) 3.4; 95% CI 1.8–6.3. In addition, older age OR 5.4 (95% CI 3.9–7.5) per 10 years, female sex OR 5.0 (95% CI 2.6–9.8) and diabetes OR 2.9 (95% CI 1.3–6.7) were strongly associated with renal impairment. The association between HIV status and renal impairment became stronger with older age (P = 0.02 for interaction). Current and nadir CD4 counts, duration of HIV infection and previous AIDS‐defining diagnosis were not associated with renal impairment among virologically suppressed PLWH.
Conclusions
The prevalence of renal impairment is low among low‐risk virologically suppressed Caucasian PLWH, but remains significantly higher than in controls. Renal impairment therefore remains a concern in all PLWH and requires ongoing attention.
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