Determinants of bone strength and fracture incidence in adult Finns: Cardiovascular Risk in Young Finns Study (the GENDI pQCT study)

Summary

Peripheral bone strength and fracture risk were studied in young adult Finns. Peripheral bone measures were associated with risk factors of osteoporosis in young adults and discriminated between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.

Purpose

This is a cross-sectional study of the determinants of bone strength and fracture risk in young Finns using peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS).

Methods

pQCT scans were performed in 1,884 subjects at distal and shaft sites of non-dominant radius and left tibia, and QUS measures (n?=?1,415) at the left calcaneus. Lifestyle factors and medical conditions affecting bone health were assessed with questionnaires.

Results

In men, the youngest age cohort had the lowest trabecular volumetric bone mineral density (vBMD) at radius and tibia (difference between the youngest and the oldest, 4.4% and 5.6%, respectively, P?<?0.001) and lowest speed of ultrasound at the calcaneus (difference 0.5%, P?=?0.016). In women, bone traits did not differ by age groups. When sexes were pooled, underweight (relative risk (RR)?=?2.95, P?<?0.001), excess alcohol intake (1.52, P?=?0.036), smoking (1.29, P?=?0.025), Crohn’s disease or inflammatory bowel syndrome (2.43, P?=?0.016), epilepsy (2.54, P?=?0.011), use of corticosteroids (2.01, P?<?0.001) and inactivity (1.34, P?=?0.045) increased the risk of low trabecular vBMD. RRs for low-energy fractures were excess alcohol intake (2.58, P?=?<0.001), anorexia (3.74, P?=?0.041) and hypogonadism (2.08, P?=?0.015). Same risk factors predicted BMD and fractures in both sexes. Trabecular bone mineral content, vBMD and bone strength index showed greatest differences (4–9%; P?<?0.05) between those with and without low-energy fractures.

Conclusions

Peripheral QCT traits are associated with common risk factors of osteoporosis in young Finns and discriminate between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.     

MRI changes and ApoE genotype, a prospective 1-year follow-up of traumatic brain injury: a pilot study

Primary objective: To examine the association between apolipoprotein E (ApoE) genotype and visibility of traumatic brain lesions during the first year after traumatic brain injury (TBI).

Research design: A prospective 1-year follow-up study in unselected victims of TBI.

Methods: The number and extent of contusions, ventricular size index and semi-quantitative score of other traumatic intraparenchymal lesions were determined with MRI ∼ 1 week and 1 year after TBI and the results were analysed in relation to the ApoE genotype in 33 patients after acute non-trivial TBI.

Results: The ApoE genotype was not associated with the visible changes occurring during this follow-up.

Conclusions: The presence of ApoE4 was not associated with MRI changes during the first year after TBI. This suggests that if the ApoE4 is associated with an unfavourable outcome after TBI, the processes responsible for the repair of visible lesions are not dependent on ApoE genotype.     

Regulation of the nitric oxide production resulting from the glucocorticoid-insensitive expression of iNOS in human osteoarthritic cartilage

OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membranes is implicated in the pathogenesis of osteoarthritis (OA) and inhibitors of NO synthesis may have indications in the treatment or prevention of joint destruction in OA. Because the signaling mechanisms as well as the NOS isoform involved in induction of NO production in human cartilage remain in many parts unclear, the present study was designed to investigate the regulation of inducible NO synthesis in human intact OA cartilage. METHODS: Cartilage specimens were collected from OA patients undergoing knee replacement surgery and studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. J774 macrophages were used for comparison as a well-documented source of iNOS. RESULTS: OA cartilage expressed iNOS and produced NO in the absence of exogenous cytokines. Addition of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS) into the culture medium enhanced NO production in a dose-and time-dependent manner. Various NOS inhibitors suppressed NO production in the following order of potency: 1400W (novel selective iNOS inhibitor)=L-NIO>L-NMMA>L-NAME. Cycloheximide (an inhibitor of protein synthesis), pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor) and genistein (an inhibitor of tyrosine protein kinases) inhibited cytokine-induced NO production, while dexamethasone, diaminohydroxypyrimidine (DAHP; an inhibitor of tetrahydrobiopterin synthesis) and PD 98059 (p42/44 MAP kinase inhibitor) had no effect. CONCLUSIONS: The results suggest that NO synthesis in human osteoarthritic cartilage derives from the glucocorticoid-insensitive expression of iNOS. Very similar mechanisms appear to regulate inducible NO synthesis in human osteoarthritic cartilage and J774 macrophages with the exception that dexamethasone inhibited NO production in J774 cells but not in osteoarthritic cartilage.     

Outcome of patients with dual diagnosis in secondary psychiatric care

Background: Dual diagnosis (DD) is a common co-morbidity of mental illness and substance use disorder (SUD) and patients with DD are prone to complications. Better knowledge on the outcome, mortality and management of patients with DD in usual secondary psychiatric care would help to inform improved treatment strategies in the future. Aims: To explore the functional outcome and mortality of patients with DD receiving psychiatric treatment. To assess the recognition of substance use disorders (SUDs) in terms of diagnosis, and the associations of clinically diagnosed SUDs with treatment-related variables. Methods: The sample of 330 patients was collected by screening all currently treated patients with the Alcohol Use Disorders Identification Test (AUDIT) and a question about other substances used. The inclusion criteria were AUDIT?>7 and/or reported use of other substances during the preceding 12 months. The Global Assessment of Functioning scale was used to assess functional outcomes during a 2-year follow-up. Information concerning treatment and patient characteristics was collected retrospectively. Results: Level of functioning remained stable among all study patients during follow-up. The mortality rate was not increased. Effective medication use was associated with improved functional outcomes. SUDs were underdiagnosed. A clinically diagnosed SUD seemed to have an impact on the regularity of appointments and the doses of prescribed medications. Conclusions: Given our results suggesting a stable level of functioning, patients with DD appear to be well managed within secondary psychiatric care. Attention should be paid to more precise diagnostics of SUDs and to effective use of medication.     

The polymorphic androgen receptor gene CAG repeat,pituitary-testicular function and andropausal symptoms in ageing men

The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.     

Musculoskeletal disorders in physically active conscripts: a one-year follow-up study in the Finnish Defence Forces

Background

Proximal humeral fractures, which occur mainly in older adults, account for approximately 4 to 5% of all fractures. Approximately 40% of these fractures are displaced fractures involving the surgical neck. Management of this group of fractures is often challenging and the outcome is frequently unsatisfactory. In particular it is not clear whether surgery gives better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform this decision.

Methods/Design

We aim to undertake a pragmatic UK-based multi-centre randomised controlled trial evaluating the effectiveness and cost-effectiveness of surgical versus standard non-surgical treatment for adults with an acute closed displaced fracture of the proximal humerus with involvement of the surgical neck. The choice of surgical intervention is left to the surgeon, who must use techniques that they are fully experienced with. This will avoid 'learning curve' problems. We will promote good standards of non-surgical care, similarly insisting on care-provider competence, and emphasize the need for comparable provision of rehabilitation for both groups of patients. We aim to recruit 250 patients from a minimum of 18 NHS trauma centres throughout the UK. These patients will be followed-up for 2 years. The primary outcome is the Oxford Shoulder Score, which will be collected via questionnaires completed by the trial participants at 6, 12 and 24 months. This is a 12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment. We will also collect data for other outcomes, including general health measures and complications, and for an economic evaluation. Additionally, we plan a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial, and their baseline characteristics, treatment preferences and intended treatment.

Discussion

This article presents the protocol for a multi-centre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.

Trial Registration

Current Controlled Trials ISRCTN50850043     

Cognitive functions in relation to MRI findings 30 years after traumatic brain injury

OBJECTIVE: The aim of the study was to relate cognitive effects of a remote traumatic brain injury (TBI) to MRI findings and severity of injury. METHOD: Sixty-one patients were assessed on average 30 years after a TBI of variable severity. A comprehensive cognitive test battery was used to evaluate memory, executive functions and cognitive overall impairment. Multiple regression analyses were used to examine the relationships between cognitive variables and MRI volumetric findings (the volumes of the hippocampus and the lateral ventricles) and local contusions on MRI. Also, the effect of injury severity on cognitive outcome was evaluated. RESULTS: Reductions in hippocampal volumes and lateral ventricular enlargement were significantly associated with impaired memory functions, memory complaints and executive functions. Of the MRI parameters used, the best predictor for cognitive outcome was the volume of the lateral ventricle. There was only a modest relationship between severity of injury and cognitive performance. CONCLUSIONS: The results show that long-term memory impairments after TBI are associated with MRI volumetric measures. This suggests that the degree of diffuse injury leading to atrophic changes is prognostically more important than the initial severity of TBI.     

Fixation of syndesmotic ruptures in 38 patients with a malleolar fracture: a randomized study comparing a metallic and a bioabsorbable screw

OBJECTIVES: To compare the performance of a metallic and a biodegradable screw in the fixation of tibia-fibula syndesmotic ruptures. DESIGN: A randomized, prospective, and blinded study. SETTING: Central hospital, Department of Surgery. PATIENTS: Forty consecutive patients with a clinically verified syndesmotic rupture in association with a malleolar fracture, of whom 38 completed the study. INTERVENTION: After syndesmosis rupture was diagnosed, implant selection was performed intraoperatively by a strict randomization with sealed envelopes. Eighteen patients were treated with a metallic screw, and 20 with a bioabsorbable polylevolactic acid screw. The metallic screws were removed in a second operation at 8 weeks postoperatively. All patients had a treatment-blinded clinical and radiographic control after a mean follow-up of 35 (range 17-51) months. MAIN OUTCOME MEASURES: Return to previous physical activity level, evaluation of ankle stability, range of motion, circumference of the ankle, and a radiographic evaluation of both ankles including a measure of the talocrural, medial joint, and syndesmotic space widths. RESULTS: More patients with a polylevolactic acid screw returned to their previous activity level, and there was less swelling in the ankles of these patients, but joint motion was similar between the groups. The mean values of syndesmotic and medial joint spaces were significantly higher in the radiographs of the operated ankles when compared to the uninjured ankle, but there was not a correlation to the type of screw used. CONCLUSIONS: Polylevolactic acid screws worked as well, or slightly better than, metallic ones in syndesmosis fixation in patients with an ankle fracture.