Boys with haemophilia have low trabecular bone mineral density and sarcopenia,but normal bone strength at the radius

Summary. Although a decreased areal bone mineral density (BMD) has been reported in patients with haemophilia, data are lacking that would reflect the three‐dimensional structure of the bone and the muscle‐bone relationship. We aimed to assess volumetric BMD, bone geometry and muscle‐bone phenotype in boys with haemophilia, and to describe the association between clinical characteristics of haemophilia and bone quality and structure. A cross‐sectional study was conducted in 41 boys with haemophilia (mean age 12.4, range 6.6–19.8 years) using peripheral quantitative CT (pQCT) at the nondominant forearm. Results were transformed into Z‐scores using previously published reference data. Significant differences were tested by one‐sample t‐test or sign test. Two‐sample t‐test and anova were used to compare results between subgroups of patients divided according to the severity of the disease, the fracture history and the number of joint and muscle bleedings. Boys with haemophilia had a decreased trabecular volumetric BMD (mean Z‐score ?0.5, P < 0.01), while their cortical volumetric BMD was increased (mean Z‐score 0.4, P < 0.05). The volumetric bone mineral content and the bone geometry at the radial diaphysis were normal when adjusted for patients’ shorter body height. Muscle area was decreased (mean Z‐score ?1.0, P < 0.001), irrespective of age. No association was observed of bone quality parameters and bone geometry with the disease severity, fracture history or number of bleedings. Bone strength measured at the diaphysis of the radius is not impaired in boys with haemophilia. The finding of the decreased trabecular bone density can be most likely attributed to their sarcopenia.     

The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N‐ (NTX‐I), C‐terminal telopeptide of type I collagen (CTX‐I) and tartrate‐resistant acid phosphatase band‐5b (TRAP‐5b), as bone resorption markers, and osteocalcin (OC) and bone‐specific alkaline phosphatase (b‐ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b‐ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 μg/L, P = 0.009), without any differences in the other BTM. NTX‐I and CTX‐I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B‐ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX‐I levels remained negatively associated with oestradiol levels, whereas b‐ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b‐ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.     

Evaluation of bone mineral density in Turkish children with severe haemophilia A: Ankara hospital experience

Summary. This study was conducted to understand the pathogenetic mechanisms that are involved in the development of bone loss in children with severe haemophilia A (HA). Fourty‐four children with severe HA and 40 age‐ and gender‐matched healthy control subjects were enrolled in this study. Markers of bone remodelling and osteoclast regulation including serum bone specific alkaline phosphatase, parathormone, 25‐hydroxy‐vitamin D₃ (25HOvitD₃), osteocalcin and calcitonin levels were studied. Bone mineral density (BMD) was also studied in all children. The measurement of markers of bone remodelling and osteoclast regulation suggested increased osteoclast‐mediated resorption activity in children with severe HA. Although serum parathormone levels were significantly increased, serum 25HOvitD₃ and osteocalcin levels were significantly reduced. BMD was significantly reduced in severe haemophilics compared with healthy controls. There was also significant inverse correlation between BMD z‐score and total joint scores, and insignificant inverse correlation between BMD z‐score and single joint scores. There were also significant inverse correlation between 25HOvitD₃ and osteocalcin levels and total joint scores. Children with severe HA could have significantly reduced BMD, compared with gender‐ and age‐matched healthy control subjects. Our results of the markers of bone remodelling and osteoclast regulation suggested that increased osteoclast‐mediated resorption and decreased osteoblastic activity in children with severe HA. All children with severe HA should be routinely screened in terms of BMD.     

Physical activity for prevention of osteoporosis in patients with severe haemophilia on long‐term prophylaxis

Summary. Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long‐term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long‐term prophylaxis to prevent bleeding. The bone density (BMD g cm⁻²) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X‐ray absorptiometry. Physical activity was assessed using the self‐report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1‐L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long‐term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis.     

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. Methods One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20–71 years underwent cross‐sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x‐ray absorptiometry. BMD data were available for 102 age‐ and gender‐matched population‐based control subjects. Results After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T‐ and Z‐scores at the hip, femoral neck and spine were lower compared with age‐matched control subjects (P ≤ 0.048). Female Type 1 patients and control subjects had similar BMDs and T‐ and Z‐scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. Conclusions Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age‐matched control subjects. Impaired bone formation may occur in Type 1 diabetes.     

Reduced bone density in patients on long‐term warfarin

Aim: Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long‐term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD. Methods: We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease ‘mechanical valve replacement’ on long‐term warfarin compared with 103 randomly selected matched controls. Results: There was a marked reduction in BMD (g/cm²) and T‐score of lumbar spine between patients and controls (P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T‐score (P < 0.03). Conclusions: Screening of patients on long‐term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium–vitamin D supplements for these patients.     

Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients

Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co‐infections. Seventy‐eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV‐HCV co‐infected, HCV mono‐infected and uninfected). The BMD was measured by dual energy X‐ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F‐BMD reduction in all the three groups, whereas L‐BMD was significantly lower in co‐infected patients (P < 0.05). The clinical score was higher in co‐infected (P < 0.002) and mono‐infected (P < 0.006). The radiological score was higher in mono‐infected than in the other two groups (P < 0.001). Overall 25‐hydroxyvitamin D (25‐OH Vit D) was reduced (87%). Bone‐specific alkaline phosphatase (b‐ALP) and telopeptide were increased in co‐infected (P < 0.001 and P < 0.01) and mono‐infected (P < 0.001 and P < 0.02). The result of the homogeneous F‐BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L‐BMD in co‐infected and the increase of b‐ALP and telopeptide in co‐infected and mono‐infected groups suggest faster bone metabolism in case of infections.     

Bone turnover markers and bone mineral density in children with haemophilia

Summary. During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross‐sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X‐ray absorptiometry and Z‐scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C‐telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm^?2) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL^?1 in the low BMD group (P = 0.012). C‐telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL^?1 in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z‐score.     

Erosive disease associated with higher bone resorption and lower bone density in women with rheumatoid arthritis

Objective: To evaluate the bone density and bone metabolism in women with rheumatoid arthritis (RA), focusing on disease activity, joint erosion, and RA‐epitope. Methods: Disease activity was assessed using erythrocyte sedimentation rate, C‐reactive protein, rheumatoid factor, Ritchie articular index (RAI), and disease activity score (DAS). The presence of joint erosion was assessed using wrist‐hand and feet X‐ray, and wrist‐hand magnetc resonance imaging. A fasting metabolic bone study was done including serum calcium, phosphate, 25(OH) vitamin D, parathyroid hormone (PTH), alkaline phosphatase (ALP), osteocalcin, and urine deoxypyridinoline/creatinine (DPD/Cr) ratio. Bone mineral density (BMD) was measured at hip, spine, distal forearm, hand, and total body using dual energy X‐ray absorptiometry (DEXA) machine. HLA‐DRB1 genes were examined using DNA sequencing based typing. Results: Seventy‐six women with RA according to 1987 American College of Rheumatology (ACR) criteria with clinical onset equal to or less than 5 years were examined. Mean (SD) of age was 55.4 (13.7) years, disease duration 34.9 (36.4) months, and 96% with ACR functional criteria class I and II. HLA typing demonstrated that 61.4% of them have the RA shared‐epitope (QRRAA or QKRAA or RRRAA) in their HLA‐DRB1 alleles. Most of them had been receiving disease‐modifying antirheumatic drugs and glucocorticoid. Erosive disease was significantly correlated with intertrochanter BMD (P = 0.044), serum calcium (P = 0.005), and urine DPD/Cr ratio (P < 0.001). Patients with erosive disease had higher DAS (P = 0.017), lower serum calcium (P = 0.006), and higher urine DPD/Cr ratio (P < 0.001). There were no statistically significant differences in serum ALP, osteocalcin, 25(OH) vitamin D, and PTH. Patients with erosive disease had lower BMD at all sites including hip, forearm, hand, lumbar spine, and total body, though only statistically significant at intertrochanter (P = 0.042). Bivariate correlation demonstrated that at all sites BMD, except femoral neck and hand BMD, negatively correlated with urine DPD/Cr ratio. Logistic regression model showed that erosive disease was a significant factor for low bone density (T‐score < ?1) at intertrochanter (OR = 6.0; 95% CI = 1.3–27.3; P = 0.020), total hip (OR = 5.5; 95% CI = 1.1–26.8; P = 0.035), and distal radius‐ulna (OR = 3.9; 95% CI = 1.1–14.0; P = 0.041). Conclusion: Patients with erosive disease demonstrated lower BMD, lower serum calcium level, and higher bone resorption. Erosive disease was a significant factor for osteopenia or osteoporosis.     

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double‐blind RCT, we randomized 81 postmenopausal osteopenic women to 1‐yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1‐yr treatment, we measured bone mineral density (BMD) by dual X‐ray absorptiometry, quantitative computed tomography (QCT), and high‐resolution peripheral QCT (HR‐pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56–73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose‐dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24‐hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1‐yr treatment with melatonin increased BMD at femoral neck in a dose‐dependent manner, while high‐dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.     

Lower bone mineral density of forearm in postmenopausal patients with radiographic hand osteoarthritis

The association between clinical parameters and forearm bone mineral density (BMD) in postmenopausal females with radiographic hand OA has not been determined. We investigated the difference in forearm BMD between radiographic hand OA and non-radiographic hand OA, and also the association between clinical parameters of patients and the level of forearm BMD. A total of 180 postmenopausal patients with hand OA were enrolled in this study. We classified them into two groups according to the Kellgren–Lawrence (K–L) radiological grade, one with radiographic hand OA (K–L grade ≥ 2) and the other with non-radiographic OA (K–L grade < 2) as controls. The number of nodal joints, swollen joints and tender joints were determined in the physical examination, and measures of BMD (g/cm²), Australian Canadian (AUSCAN) OA hand index, grip strength, pinch strength, and visual analogue scale (VAS) were also estimated. Patients with radiographic hand OA had lower distal radius BMD when compared with controls (0.35 ± 0.06 vs. 0.40 ± 0.05, P < 0.001). After adjusting for variables such as age, menopausal duration, number of nodal joints, and AUSCAN function index, the difference in BMD between the two groups was also significantly different (0.35 ± 0.04 vs. 0.38 ± 0.04, P < 0.001). For analysis of risk factors for forearm BMD in hand OA, age and K–L OA grade in total hand OA are considered risk factors, whereas age and menopause duration contribute to the forearm BMD in radiographic hand OA patients (P < 0.001, P = 0.002, respectively). The development of osteoporosis at the distal radius in radiographic hand OA is associated with older age (OR = 1.216, P = 0.002), lower BMI (OR = 0.777, P = 0.004) and lower stiffness in the AUSCAN OA index (OR = 0.505, P = 0.003). This study shows that the BMD levels of the distal radius in patients with radiographic hand OA are significantly lower when compared to those of controls. Forearm BMD levels are positively associated with age and K–L radiological grade in total hand OA, whereas age and menopausal duration are closely related with radiographic hand OA. The presence of osteoporosis in the distal radius in radiographic hand OA may be influenced by age, BMI, and stiffness on the AUSCAN index.     

Bone density and health‐related quality of life in adult patients with severe haemophilia

Summary. Severe haemophilia and reduced bone density can negatively influence perception of patient’s health‐related quality of life (HRQoL), especially considering future aspects, the risk of losing independence or pain suffering. The aim of this study was to assess levels of HRQoL in severe haemophilia patients and to compare HRQoL to those of the general population as well as to determine whether reduced bone density is correlated to the perceived HRQoL. Patients were divided into two groups based on timing of being treated with prophylaxis: Group A (started prophylaxis at age of ≤3 years; n = 22); Group B (at age of >3 years; n = 15). The bone mineral density (BMD g cm^?2) of different measured sites was measured by dual energy X‐ray absorptiometry (DXA). HRQoL was assessed using SF‐36 questionnaire. Group A have mean BMD T‐score >?1.0 (i.e. normal score) at all measured sites, and have almost similar scores in the SF‐36 domains compared with the reference population. Group B have mean BMD T‐score ?1.0 at lumbar spine and total body, and their scores in the SF‐36 domains were lower compared with the reference population. Moreover, significant correlations were found between BMD at femoral neck and total body with physical domains. With adequate long‐term prophylaxis since early childhood, adult patients with haemophilia report a comparable BMD and HRQoL to the Swedish reference population. Reduced BMD in group B correlated with impaired physical health, which underscores the importance of early onset of adequate prophylactic treatment.     

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.     

Bone mineral density in children with cirrhosis

Background Despite the clinical importance of osteoporosis in individuals with cirrhosis, little is known about it, especially in children. We evaluated the bone mineral density (BMD) and bone mineral content (BMC) of children with cirrhosis. Methods Forty children with cirrhosis (mean age, 10.4 ± 3.9 years) were involved. BMD and BMC were measured by dual energy X-ray absorptiometry at lumbar vertebrae 1–4, and the results were compared with those of 62 healthy age- and sex-matched children. Results The mean lumbar spine BMD of patients with cirrhosis was 0.482 ± 0.107 g/cm² and that of the controls was 0.687 ± 0.172 g/cm² (P < 0.0001). The mean lumbar spine BMC of patients with cirrhosis was 20.008 ± 8.409 g and that of controls was 32.859 ± 14.665 g (P < 0.0001). After the confounding variables (weight, height, and pubertal stage) were controlled for, the difference in BMD and BMC values between patients with cirrhosis and healthy controls was significant (0.535 ± 0.061 g/cm² vs 0.653 ± 0.048 g/cm², and 24.515 ± 5.052 g vs 29.952 ± 3.971 g, respectively). Conclusions Because of the significant difference in BMD and BMC values between our patients with cirrhosis and healthy controls, patients with cirrhosis should be evaluated for osteopenia.     

Oral health status in children and adolescents with haemophilia

This case‐controlled study aimed to evaluate the existing oral health status in children and adolescents with haemophilia. A total of 50 haemophilia patients and 50 matched controls aged seven to 16 years were recruited into the study. Clinical examination was carried out to determine dental caries experience, oral hygiene status and gingival condition in these two groups. Information regarding previous dental history, oral hygiene practices and dietary habits were also obtained. No significant difference was found in mean caries experience in primary and secondary dentitions (P = 0.86 and 0.32) and in Simplified Oral Hygiene Index (OHI‐S, P = 0.20) between both groups. However, a significantly higher proportion of haemophilia patients (24%) had better oral hygiene status as compared to the controls (2%, P = 0.004). Furthermore, there was a significant difference in Modified Gingival Index (MGI, P = 0.02) between the two groups with the study group having less gingival inflammation. A total of 88% (n = 44) of the haemophilia patients were registered and received dental treatment in specialist dental clinics. More than half (56%, n = 28) had frequent dental visits and only one‐third of the haemophilia patients had history of hospitalization due to oral problems. There was no significant difference in oral hygiene practices and dietary habits between both groups. In general, haemophilia children and adolescents in this study had similar caries experience, a significantly better oral hygiene status and gingival health as compared to healthy controls. The main reason for this is the multidisciplinary approach implemented by medical health‐care professionals as primary care provider and the dental team.     

A longitudinal study of family structure in Swedish persons with haemophilia

Haemophilia is an X‐linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age‐ and gender‐matched controls. The national Multi‐Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.     

A case–control study assessing bone mineral density in severe haemophilia A in the UK

It has been shown that bone mineral density (BMD) may be lower in patients with haemophilia (PWH). A comparison to control subjects is required to thoroughly assess current BMD in PWH in the UK. The objective of this study was to test the hypothesis that BMD is lower in PWH than in controls, and in patients with more severely affected joints or lower activity levels. In this case–control study, 37 patients with severe haemophilia A were recruited from two haemophilia centres in the UK. A group of 37 age, gender and ethnicity‐matched control participants were recruited. All participants had a bone density scan, a musculoskeletal assessment, a blood test for vitamin D and completed a functional activity questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than expected for age. No control participants had osteoporosis, 3% had osteopenia and 14% had BMD lower than expected for age. Ninety one per cent of case participants and 92% of control participants had reduced 25(OH)D levels. Case participants had significantly lower BMD than control participants, and case participants with more severely affected joints, lower activity levels, HIV, history of hepatitis C or lower BMI had significantly lower BMD. Patients with severe haemophilia have a higher risk of low BMD than men without haemophilia. Patients with more severely affected joints and lower activity levels have lower BMD. It remains unclear whether patients with low BMD reached adequate peak bone mass. Low vitamin D may be present in the majority of PWH.     

Somatosensory profile of patients with haemophilia

Introduction

Patients with haemophilia (PwH) suffer from an enhanced pain sensitivity due to repetitive joint bleedings. A comprehensive, quantitative examination of the somatosensory system has not been performed in this population to date.

Material and methods

Thirty patients with moderate or severe haemophilia A or B and 30 healthy controls were examined by means of Quantitative Sensory Testing to assess the function of the somatosensory system. Detection (DT) and pain thresholds (PT) were determined, amounting to a total of 13 parameters. Both knee joints and the hand as reference were examined in order to assess both joint‐specific as well as general changes in the somatosensory profile.

Results

Analysing DT and PT, a significant main effect was found for group × stimulus interaction (P ≤ .001). Post hoc tests revealed significant differences in DT between PwH and controls for thermal stimuli across both knees (cold DT: P < .001; warm DT: P < .01) and the hand (cold DT: P < .01; warm DT: P < .05). Mechanical DT was increased in PwH at both knee joints (left knee: P ≤ .05; right knee: P ≤ .01). Furthermore, pressure PT was decreased in PwH at both knees (P ≤ .001).

Conclusion

Haemophilic arthropathy leads to alterations of the somatosensory profile in PwH. Our results reveal initial evidence of a combination of peripheral sensitization, indicated by decreased pressure PT and mechanical DT at the knee joints, as well as general changes of the somatosensory system, shown by reduced thermal DT at affected sites and remote from these. Therefore, both mechanisms have to be considered regarding the pain management in PwH.     

Relation between calcium intake,grip strength and bone mineral density in the forearms of girls aged 13 and 15

Abstract. Objectives. To evaluate whether there is an association between calcium intake in adolescent girls and bone mineral density (BMD). Also, the relationships between BMD, various anthropometric factors and grip strength were evaluated. Design. Cross-sectional comparison of BMD, calcium intake and grip strength in 13 and 15 year age groups, randomly selected. Setting. Ten secondary elementary schools in the Reykjavik area. Subjects. One hundred and ninety-seven Icelandic Caucasian girls aged 13 and 15. One hundred and seventy participated and 162 completed the study. Main outcome measures. Single photon absorptiometry was used to measure BMD and bone mineral content (BMC) in both forearms. Consumption of milk and dairy products was assessed using a food frequency questionnaire. Height and weight were measured and grip strength was determined with a hand-held dynamometer. Results. Calcium intake was found to be significantly correlated to BMD in the older group after adjustment for menarcheal age and weight (r = 0.24; P < 0.05). Division into three subgroups yielded a significantly greater coefficient of correlation between calcium intake and BMD in the lowest calcium consumption group (r = 0.44; P < 0.05). No association was found in the younger age group. Significant positive correlations between grip strength and regional bone mineral density accounted for up to 16.8% of the variation in BMD (P < 0.001) and 38.4% of the variation in BMC. Conclusions. This study is consistent with the hypothesis that a threshold effect of calcium intake on BMD might exist. Above this threshold (1000–1200 mg) no further effect on BMD was seen. The results show a strong association between grip strength, a measure representative of total body strength, and BMD.     

Hypercalciuria and kidney function in children with haemophilia

Adults with haemophilia have a higher incidence of chronic kidney disease than general male population. We recently showed that children with haemophilia have higher urinary calcium excretion and lower whole body bone mineral density than controls in spite of prophylaxis with the deficient coagulation factor concentrate, serum vitamin D concentrations comparable to those of healthy children and physically active lifestyle. Persistent hypercalciuria may result in nephrocalcinosis and impact renal function. This study sought to assess persistence of urinary calcium excretion and kidney function in children with haemophilia. We investigated retrospectively urinary calcium excretion in 30 children with haemophilia (mean age 12.5 years) from consecutive urine samples over a 2‐year period. Renal evaluation included blood and urine specimen, blood pressure, and renal ultrasound. High number of children with haemophilia had intermittent hypercalciuria. Hypercalciuria was not associated with age, severity of haemophilia or previous hypercalciuria. Kidney function and renal ultrasound were normal with the exception of suspected kidney stone in one patient with haemophilia and transient hypercalciuria. Vitamin D concentrations improved after the families had received information and recommendations concerning vitamin D substitution. Our findings indicate that haemophilia per se predisposes to hypercalciuria which may in turn affect bone mineral content and kidney function. Whether childhood‐onset intermittent hypercalciuria contributes to hypertension and renal complications in adulthood remains to be elucidated in future studies.