Prescribing a website.

AIM: To assess the value of directing the attention of patients to sources of medical information on the internet. DESIGN: Prospective qualitative study in an orthopaedic outpatient clinic. PARTICIPANTS: 253 patients agreed to complete electronic questionnaires before and after reviewing information relevant to their conditions on the internet. Patients were allocated randomly into two groups; one group was given indications of general sites and the other recommended specific non-commercial sites. Completed questionnaires were received from 44 patients. RESULTS: 95% of the patients found the internet information easy to understand and 84% said that it was helpful for coping. 86% of the patients were satisfied that their current treatment was appropriate in the light of what they had learned from the internet. Ten patients out of the 36 who expressed a view thought that the internet information contradicted that provided by the doctor. Despite these results most patients still said that the doctor represented the best source of patient education. CONCLUSIONS: Increasing numbers of patients are familiar with the internet. Most of our patients felt that the internet was, on balance, helpful in providing information. The main difficulties with the internet are the sheer volume of information, the potential for misleading and the danger of misunderstanding. We feel that there is a real place for the specific prescription of an internet site by a clinician who has personally reviewed it to a patient thought to be able to benefit from it.

Bone health in patients with fibromyalgia.

OBJECTIVES: To determine whether women with fibromyalgia are at increased risk of developing osteoporosis or osteomalacia. METHODS: Forty premenopausal women with fibromyalgia and 37 age-matched female controls were studied. Broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were measured at the calcaneum and bone mineral density was measured at the forearm and lumbar spine using dual-energy X-ray absorptiometry. Serum calcium, alkaline phosphatase, gamma-glutamyl transferase, 25-hydroxyvitamin D and plasma viscosity were measured in all subjects and parathyroid hormone was measured in subjects recruited in the latter part of the study. RESULTS: Seventeen patients with fibromyalgia syndrome and seven controls had 25-hydroxyvitamin D concentrations <20 nmol/l (P < 0.015) and in three FMS patients serum parathyroid hormone was raised. Bone density in fibromyalgia patients was slightly lower at the mid-distal forearm but comparable to that in controls at other sites. CONCLUSIONS: There is no reason to recommend routine bone densitometry in fibromyalgia patients. However, vitamin D subnutrition is common in these patients and this should be sought.

Peripheral bone mineral density in patients with distal radial fractures.

Fractures of the distal forearm are widely regarded as the result of "fragility". We have examined the extent to which patients with Colles' fractures have osteopenia. We measured the bone mineral density (BMD) in the contralateral radius of 235 women presenting with Colles' fractures over a period of two years. While women of all ages had low values for ultra-distal BMD, the values, in age-matched terms, were particularly low among premenopausal women aged less than 45 years. This result was not due to the presence of women with an early menopause. This large survey confirms and extends the findings from earlier small studies. We consider that it is particularly important to investigate young patients with fractures of the distal forearm to identify those with osteoporosis, to seek an underlying cause and to consider treatment.

Severe symptomatic osteoporosis in patients on androgen deprivation therapy for prostatic carcinoma.

We report 3 patients referred to the bone clinic after spinal fractures. Dual energy X-ray absorptiometry showed severe osteoporosis. Each patient was found to have a history of prostatic carcinoma and long-term treatment with goserelin. We suggest that all patients who have received androgen deprivation therapy for more than 1 year should be evaluated by bone densitometry.

Musculo-skeletal problems associated with pregnancy in women with osteogenesis imperfecta.

Having seen a number of women with osteogenesis imperfecta who developed severe back pain during or just after pregnancy, we wished to determine the likelihood of this and other musculoskeletal problems in pregnancy. We interviewed by telephone 100 women with osteogenesis imperfecta who had, between them, 213 pregnancies between 1957 and 1998. For each pregnancy we recorded the Sillence type for the osteogenesis imperfecta, the mode of delivery and the musculo-skeletal complications. The most common problem was back pain, which was severe in or after 28 pregnancies (13.1%). There was no identifiable relationship to the type of osteogenesis imperfecta or to the mode of delivery. In many cases the back pain could be related to crush fractures of vertebrae. Other problems identified included spinal deformity, non-vertebral fractures, disc problems and ligament problems. We suggest that it may be appropriate to advise the avoidance of long periods of breast feeding in women with OI, particularly in those who have vertebral fractures.

Mortality in various types of osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of closely related inherited diseases characterized by abnormal bone fragility. The current clinical classification system delineates 6 types, one of which (type II) is so severe that mortality is 100%, either intrauterine or perinatal. The types are differentiated by clinical groups, by severity, and by the presence or absence of other features such as blue sclerae or dentinogenesis imperfecta. There are no known previous studies of mortality in OI. RESULTS: From a registry created in association with the Brittle Bone Society, 743 patients with OI in England and Wales were observed in the period 1980-1993. These were classified into 3 groups (type IA, type III, and types IB, IVA, and IVB combined). Average annual mortality rates were determined in each group by sex and attained age. These rates were compared with 1981 rates in the population of England and Wales, matched by sex and age. Results are given in terms of exposures, observed and expected deaths, and 2 indices of excess mortality: mortality ratios and excess death rates per 1000 person-years. CONCLUSION: In type IA, 51.5% of the OI cases overall, there was no significant excess mortality (mortality ratio 108%, based on 15 deaths). In type III, on the other hand, excess mortality was very high in children and still significantly high at ages 15-34 years. In the combined group of types IB, IVA, and IVB, the mortality ratio was 157% in patients aged 45 and up (not significant at the 95% confidence level), but higher ratios at younger ages were significant, even though based on a total of only 5 deaths.

Excess paternal age in apparently sporadic osteogenesis imperfecta.

The objective of this study was to examine whether parental age is associated with the occurrence of apparently sporadic osteogenesis imperfecta (OI). We compared parental age and the joint distribution of maternal and paternal age with expected distributions based on statutory birth records for each year and location of birth. The study included patients with OI based in the United Kingdom. The study was restricted to cases born in England, Wales, and Scotland between 1961 and 1998. Subgroup analysis was by clinical type [Sillence et al., 1979: J Med Genet 16:101-116] and apparent mode of inheritance based on pedigree analysis. Of 730 eligible cases, 357 were apparently sporadic. The mean age of fathers at birth of children with apparently sporadic OI was 0.87 years greater than expected (P = 0.010; 95% confidence interval = 0.21 to 1.54 years). The relative risk was 1.62 for fathers in the highest quintile of paternal age compared with fathers in the lowest quintile. The magnitude of the paternal age excess did not differ significantly between Sillence types (analysis of variance P = 0.534). In sporadic cases, paternal age was 0.51 years greater than expected, given maternal age, year, and location of birth (P = 0.033). In contrast, in familial cases, there was no significant paternal age excess, and paternal age was not significantly different from that expected given maternal age. Increased paternal age is a significant risk factor for sporadic OI. This effect is not accounted for by increasing maternal age. The magnitude of the paternal age excess is small in comparison with that in some other autosomal dominant disorders.

How common is hearing impairment in osteogenesis imperfecta?

Hearing impairment has long been recognized as a common feature in osteogenesis imperfecta. The figures in some publications could be taken to imply that, with increasing age, the proportion of osteogenesis imperfecta patients with hearing impairment approaches 100 per cent. The incidence of hearing loss in a large survey of 1394 patients with osteogenesis imperfecta was examined. It was found that the most common age of onset was in the second, third and fourth decades of life. At the age of 50 approximately 50 per cent of the patients had symptoms of hearing impairment; over the next 20 years there was little further increase. Differences were shown between patients with different clinical types of osteogenesis imperfecta as delineated in the Sillence classification; hearing loss was significantly less common in the type IV disease than in the type I disorder. Among the 29 families with osteogenesis imperfecta type IA there were distinct differences in the likelihood of hearing loss. These findings provide insights which will be valuable in giving patients advice on the likelihood of developing hearing loss in the future.

Bone mineral density of the radius in patients with Colles' fracture.

To ascertain whether patients with Colles' fracture should be investigated for osteoporosis and the risk of future fractures, we measured the bone mineral density of the distal radius of the other arm in 31 women patients and compared the results with those of a control group of 289 normal women. We divided the patients into two groups, those younger than 66 years and those older. In 25 patients we found values for bone mineral density which were lower than one standard deviation below the mean value for their age. Younger patients had a deficit greater than that expected for their ages. We believe that women with Colles' fracture should be evaluated routinely for osteoporosis, particularly if they are under 66 years of age.

Prediction of bone strength from cancellous structure of the distal radius: can we improve on DXA?

Recent studies show that structural parameters of bone, obtained from computerized image analysis of radiographs, can improve the noninvasive determination of bone strength when used in conjunction with bone density measurements. The present study was designed to assess the ability of image features alone to predict the mechanical characteristics of bones. A multifactorial model was used to incorporate simultaneously a number of characteristics of the image, including periodicity and spatial orientation of the trabeculae. Fifteen pairs (29 specimens) of unembalmed human distal radii were used. The cancellous bone structure was determined using computerized spectral analysis of their radiographic images and the bones were tested to failure under compression. Multilayered perceptron neural networks were used to integrate the various image parameters reflecting the periodicity and the spatial distribution of the trabeculae and to predict the mechanical strength of the specimens. The correlation between each of the isolated image parameters and bone strength was generally significant, but weak. The values of mechanical parameters predicted by the neural networks, however, had a very high correlation with those observed, namely 0.91 for the load at fracture and 0.93 for the ultimate stress. Both these correlations were superior to those obtained with dual-energy X-ray absorptiometry and with the cross-sectional area from CT scans: 0.87 and 0.49 respectively. Our observation suggests that image parameters can provide a powerful noninvasive predictor of bone strength. The simultaneous use of various parameters substantially improved the performance of the system. The multifactorial architecture applied is nonlinear and possibly more effective than traditional multicorrelation methods. Further, this system has the potential to incorporate other non-image parameters, such as age and bone density itself, with a view to improving the assessment of the risk of fracture for individual patients.

Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.

Pseudovitamin D-defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1alpha-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain. The two cases in the third kindred were compound heterozygotes with missense mutations in exons 6 and 9. We have also identified a C/T polymorphism in intron 6 of the P450c1 genomic DNA. Interferon gamma-inducible 1-OHase activity in blood-derived macrophages was shown by 1,25(OH)2D synthesis in all control cells tested (37-184 fmol/h/106 cells) and those from the PDDR family parents (34-116 fmol/h/106 cells) but was totally absent from the patients' cells, indicating a defect in their macrophage 1-OHase, similar to the presumed renal defect. The assumption of similarity between the renal and macrophage P450c1 was supported by our ability to clone a 514 bp sequence, including the heme-binding region of the macrophage P450c1 cDNA from controls, which was identical to that published for both the renal and keratinocyte P450c1 cDNAs.

A randomized comparison of driver reaction time after open and endoscopic tension-free inguinal hernia repair.

BACKGROUND: The aim of this study was to assess whether prosthetic tension-free inguinal hernia repair would cause less impairment of reaction times, thus allowing an earlier return to driving than previously recommended after conventional hernia repair. METHODS: Driver reaction times were measured in 64 patients randomized to open tension-free repair or totally extraperitoneal endoscopic inguinal hernia repair. Measurements were made preoperatively and on postoperation days 1, 3, and 6. RESULTS: In the endoscopic group, there was a gradual improvement in hand and foot reaction times over the days tested. In the open group, there was a slowing in both hand and foot reaction times on postoperation days 1 and 3. The difference in foot reaction times between the open and endoscopic groups was significant on these days (p = 0.01 and 0.003, respectively). By day 6, the foot reaction times in the open group were slightly faster than before surgery. CONCLUSIONS: After prosthetic tension-free inguinal hernia repair, patients can return to driving 1 week after the operation.

Evaluation of peripheral dual energy X-ray absorptiometry: comparison with single photon absorptiometry of the forearm and dual energy X-ray absorptiometry of the spine or femur.

An evaluation of the Osteoscan peripheral dual energy X-ray absorptiometer (pDXA) was carried out to compare its performance with those of a single photon absorptiometer (SPA) (Molsgaard Medical ND1100A) and a dual energy X-ray absorptiometer (DXA) (Lunar DPX alpha) of the spine or femur. In 57 patients, correlation between bone mineral content (BMC) of the forearm at the ultradistal (UD) site by pDXA and by SPA was high (r = 0.94). Comparisons were also made with spine and femur bone mineral density (BMD) DXA measurements. The correlation of z-scores of UD BMD with z-scores for lumbar spine L2-L4 was r = 0.63 (n = 73 patients); and with z-scores for neck of femur was r = 0.72 (n = 33). With the Osteoscan the measurement error coefficient of variation in vivo was 2.6% for BMC, 1.8% for BMD at the ultradistal site; 2.1% for BMC and 1.9% for BMD at the mid-distal site. Repeat measurements were made of the European forearm phantom; precision for SPA was slightly better than either pDXA or Lunar DXA. The Osteoscan has the potential for a rapid throughput of patients and is not affected by calcification and degenerative changes that can corrupt DXA measurements on the anteroposterior spine in older women.

Influence of injection site for low-dose heparin on wound complication rates after inguinal hernia repair.

A high incidence of complications related to bleeding was observed after open prosthetic inguinal hernia repair. The site of injection of low-dose heparin into the abdominal wall was thought to be a possible causal factor for these complications. The wound complication rate after repair of primary unilateral inguinal hernias was recorded for 51 patients who had been given abdominal wall injections of heparin. Subsequently the injection site was changed to the upper limb in a further 63 patients and the incidence of wound complications recorded. A significantly higher incidence of haematomas and seromas was found in the abdominal wall injection group (39.2% vs 17.5%, P = 0.01). The role of low-dose heparin prophylaxis in inguinal hernia repair is discussed. We conclude that in those patients receiving heparin prophylaxis the injections should be given at a site remote from the operative area.

Skin content of 7-dehydrocholesterol in patients with malabsorption.

The mechanism for the development of vitamin D deficiency in patients with malabsorption remains unclear. We wished to examine the hypothesis that one factor was a reduced skin content of 7-dehydrocholesterol, the precursor for the formation of vitamin D in the presence of ultraviolet radiation. We measured 7-dehydrocholesterol in skin samples from 9 patients who had previously had vitamin D deficiency due to malabsorption (6 with Crohn's disease, 2 with primary biliary cirrhosis, and 1 with idiopathic pseudo-obstruction). We found no evidence of reduced levels of 7-dehydrocholesterol in the skin in these patients. Lack of 7-dehydrocholesterol does not contribute to vitamin D deficiency in malabsorption.

Osteogenesis imperfecta and other heritable disorders of bone.

This chapter summarizes the many recent advances in our understanding of the principal heritable disorders of bone. In the course of little more than a decade many diseases that were recognizable only by their clinical and radiological features have become explicable in molecular terms. Large numbers of mutations of the genes coding for collagen, for alkaline phosphatase, for the cell surface receptors for parathyroid hormone and for calcium, and for a number of other proteins, are recognized. The chapter covers the many variants of osteogenesis imperfecta, the most common heritable cause of fractures. It also covers osteopetrosis, hypophosphatasia, pseudohypoparathyroidism (with Albright's hereditary osteodystrophy), familial benign hypercalcaemia, autosomal dominant hypocalcaemia and the molecular causes of some chondrodysplasias.

Causes of death in osteogenesis imperfecta.

AIMS: To determine the causes of death in patients with osteogenesis imperfecta, excluding infants with the perinatal lethal form (type II). METHODS: Seventy nine patients with known osteogenesis imperfecta were identified, 37 of whom had been seen clinically in life. Causes of death were identified from death certificates, postmortem reports, medical records, hospital consultants, relatives, and the Brittle Bone Society's records. RESULTS: Patients with the milder types of osteogenesis imperfecta, I and IV, often had a normal lifespan and died of unrelated illnesses such as myocardial infarction and malignancy. In some of these patients and in many patients with the more severe type III disease, it was clear that osteogenesis imperfecta contributed significantly to death, almost certainly to many of the respiratory deaths and to deaths from cardiac failure due to kyphoscoliosis. Osteogenesis imperfecta also caused six deaths, directly or indirectly, due to basilar invagination of the skull. Osteogenesis imperfecta may have contributed to deaths from intracranial bleeding. Apparently minor traumatic incidents may have disastrous consequences in patients with this disorder. CONCLUSIONS: Prompt care for respiratory infections and prevention of trauma in patients with osteogenesis imperfecta is essential.