Search for secondary osteoporosis: are Z scores useful predictors?

AIM: To determine whether Z scores can be used to predict the likelihood of patients having a secondary cause of low bone mineral density. METHODS: A retrospective cross sectional study was conducted among 136 consecutive patients with osteoporosis at Ninewells Hospital, Dundee, UK, between 1998-2002. RESULTS: 20.5% of female patients in this study were identified with previously unrecognised contributors to the low bone mineral density. In women, at a Z score cut-off of -1, the sensitivity of detecting a secondary cause for osteoporosis is 87.5% with a positive predictive value of 29.2%. CONCLUSION: In women, a Z score of -1 would identify a majority of patients with a secondary cause for low bone mineral density and identifies patients who would especially benefit from a thorough history and clinical examination.

Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health?

BACKGROUND: The role of nutritional influences on bone health remains largely undefined because most studies have focused attention on calcium intake. OBJECTIVE: We reported previously that intakes of nutrients found in abundance in fruit and vegetables are positively associated with bone health. We examined this finding further by considering axial and peripheral bone mass and markers of bone metabolism. DESIGN: This was a cross-sectional study of 62 healthy women aged 45-55 y. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck and by peripheral quantitative computed tomography at the ultradistal radial total, trabecular, and cortical sites. Bone resorption was calculated by measuring urinary excretion of pyridinoline and deoxypyridinoline and bone formation by measuring serum osteocalcin. Nutrient intakes were assessed by using a validated food-frequency questionnaire; other lifestyle factors were assessed by additional questions. RESULTS: After present energy intake was controlled for, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass by Pearson correlation (P < 0.05 to P < 0.005). Femoral neck BMD was higher in women who had consumed high amounts of fruit in their childhood than in women who had consumed medium or low amounts (P < 0.01). In a regression analysis with age, weight, height, menstrual status, and dietary intake entered into the model, magnesium intake accounted for 12.3% of the variation in pyridinoline excretion and 12% of the variation in deoxypyridinoline excretion. Alcohol and potassium intakes accounted for 18.1% of the variation in total forearm bone mass. CONCLUSION: The BMD results confirm our previous work (but at peripheral bone mass sites), and our findings associating bone resorption with dietary factors provide further evidence of a positive link between fruit and vegetable consumption and bone health.

Estimating the point accuracy of population registers using capture-recapture methods in Scotland.

STUDY OBJECTIVE: To estimate the point accuracy of adult registration on the community health index (CHI) by comparing it with the electoral register (ER) and the community charge register (CCR). DESIGN: Survey of overlapping samples from three registers to ascertain whether respondents were living at the addresses given on the registers, analysed by capture-recapture methods. SETTING: Aberdeen North and South parliamentary constituencies. PARTICIPANTS: Random samples of adult registrants aged at least 18 years from the CHI (n = 1000), ER (n = 998), and CCR (n = 956). MAIN RESULTS: Estimated sensitivities (the proportions of the target population registered at the address where they live) were: CHI--84.6% (95% confidence limits 82.4%, 86.7%); ER--90.0% (87.5%, 92.5%), and CCR--87.7% (85.3%, 90.3%). Positive predictive values (the proportions of registrants who were living at their stated addresses) were: CHI--84.6% (82.2%, 87.0%); ER--94.0% (90.9%, 97.1%), and CCR--93.7% (91.7%, 95.7%). CONCLUSIONS: The CHI assessed in this study was significantly less sensitive and predictive than the corresponding ER and CCR. Capture-recapture methods are effective in assessing the accuracy of population registers.

Age-related changes in cerebrospinal fluid protein concentrations.

The blood-brain barrier (BBB) has a key role in CSF homeostasis and preservation of normal neuronal function. There has been little investigation of changes in barrier function in elderly subjects without evidence of neurological disease. The ageing brain demonstrates increased vulnerability to a variety of insults, which may reflect a deterioration in barrier performance. Direct measurement of BBB function is difficult but the CSF/serum quotients of individual proteins is the most widely used parameter. The present study sought age related changes in the CSF/serum quotients of prealbumin, albumin, immunoglobulin G and alpha 2-macroglobulin in adults with no neurological deficit. A prospective study was established, and 107 subjects (aged 18-89 yrs) were recruited from patients undergoing spinal anaesthesia or diagnostic myelography. A weak but significant positive correlation was found between the CSF/serum quotients and age for all the proteins studied, but with the exception of alpha 2-macroglobulin, these changes probably reflect age related falls in serum protein concentrations found in this study. alpha 2-Macroglobulin appears to be a sensitive indicator of barrier function for large populations, suggesting a subtle decline of BBB integrity with increasing age. This may be a true age-related change or could reflect an increased incidence of subclinical disease in an ageing population.

The climacteric, osteoporosis and hormone replacement; views of women aged 45-49.

We report climacteric symptoms among women aged 45-49, and their attitudes towards HRT and osteoporosis prevention. Semi-structured questionnaires were administered to 481 women attending for bone density screening after random invitation. We recorded social class, menopausal status, history of HRT exposure and climacteric symptoms, awareness of HRT and osteoporosis, and potential willingness to consider HRT before and after bone densitometry. In total, 294 (61%) were from non-manual social classes; 338 (70%) were premenopausal, 68 (14%) postmenopausal and 75 (16%) uncertain; 101 (21%) were current/previous HRT users. Three or more climacteric symptoms were experienced by 189 (56%) of premenopausal women, compared to 64 (94%) of postmenopausal women. Most women had heard of HRT (96%) and osteoporosis (84%), usually from women's magazines or friends. HRT was usually prescribed for climacteric symptoms and, in one case, for osteoporosis prevention. Side effects were reported with most HRT preparations and affected 38% of all users. Of the 380 (79%) women who had never taken HRT, half had concerns about such treatment, and few wanted it at the menopause. However, 364 (96%) said they would consider HRT if their bone scan suggested increased osteoporosis risk. In conclusion, women around the menopause experience considerable climacteric morbidity, but are often anxious about HRT use. Better health education might improve HRT uptake, while long-term compliance might be enhanced by disclosure of fracture risk.

Perimenopausal bone density screening--will it help prevent osteoporosis?

OBJECTIVE: To estimate the potential efficacy and cost-effectiveness of hormone replacement therapy (HRT) in the prevention of osteoporotic fractures, with and without the assistance of perimenopausal bone mineral density (BMD) screening. METHOD: Residual lifetime fracture experience of a hypothetical cohort of 100,000. British women aged 45 years at baseline, modelled using prevailing UK mortality and fracture rates. Appropriate fracture risk gradients were used to estimate the distribution of future fragility fractures (distal forearm, proximal femur and clinically diagnosed vertebral fractures) according to quarters of baseline bone density measured at fracture specific sites. We assumed that 72% of the population could be contacted and would attend for HRT counselling, with or without bone densitometry, that 10 years of continuous HRT use would reduce fracture rates by 50%, and that compliance with HRT might vary between 10% and 50%. Universal recommendation of HRT was compared to selective treatment protocols offering HRT to those women whose BMD fell below the 25th, 50th or 75th percentile of BMD at the lumbar spine, femoral neck or distal forearm, measured either singly or in combination. RESULTS: The proportion of future fractures averted was closely related to compliance with therapy, but for any given level of compliance, universal treatment always achieved the greatest reduction in fractures. If compliance was 10% universal HRT was also the most cost-effective strategy, but if compliance was higher or if the unit cost of HRT increased, selective strategies were often more cost-effective. The sensitivity of BMD screening in identifying women at risk of future fracture could be increased by relaxing the BMD decision threshold, or expanding the number of skeletal sites measured, or both. However increments in test sensitivity were always accompanied by reductions in specificity. CONCLUSIONS: If BMD measurement does not influence compliance, then universal treatment with HRT is likely to prevent more fractures, at a similar or lower average cost per fracture averted, than selective therapy. However, if BMD screening leads to increased compliance, or if more expensive forms of treatment were used, then our model suggests a favourable impact of screening on the numbers and/or net cost of fractures prevented.

Recruitment methods for screening programmes: trial of a new method within a regional osteoporosis study.

OBJECTIVE: To estimate the response rates and operating costs of three recruitment methods within a regional osteoporosis screening programme. DESIGN: Randomised trial of three types of invitation letter: one offering fixed appointments with option to change time, one offering fixed appointments but requiring telephoned confirmation of intention to attend, and one inviting recipient to telephone to make an appointment. SETTING: Osteoporosis screening unit, Aberdeen. SUBJECTS: 1200 women aged 45-49 years living within 32 km of Aberdeen and randomly selected from the community health index. 400 women were randomised to each appointment method. MAIN OUTCOME MEASURES: Numbers attending for screening; default rate among women who confirmed appointments; social class of attenders; cost per appointment slot and per completed scan. RESULTS: 299 (75%), 277 (69%), and 217 (54%) women were scanned after fixed, confirmable, and open invitations respectively. Women who attended were given a questionnaire, and 694 (87.5%) returned it. No significant differences were found in the social class of attenders among the three methods. Of the 514 women who made or confirmed appointments, 494 attended for a scan. Total costs per scan were 25.00 pounds, 21.40 pounds, and 21.00 pounds for fixed, confirmable, and open invitations respectively. CONCLUSIONS: The offer of a fixed appointment requiring telephoned confirmation has the potential to reduce the costs of scanning without exaggerating any social bias or significantly reducing response rates provided that empty appointments can be rebooked at short notice.

Incidence of serious side effects with intravenous bisphosphonate: a clinical audit.

BACKGROUND: Bisphosphonates (BP) have been associated with osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). The prevalence of these side effects in intravenous (IV) BP-treated subjects is not well understood. AIM: This audit aimed to delineate the prevalence of ONJ, thigh pain and AFF in patients having regular IV BP and its effect on bone mineral density (BMD). Design and METHODS: Patients attending for IV BP over a 3-month period completed a questionnaire about thigh pain and dental health. Data concerning BMD, treatment indication and treatment history were obtained from medical records. RESULTS: There were 201 patients between 28 and 94 years (74.1% female) mostly on zoledronate (ZOL) (102) or pamidronate (PAM) (97). Osteoporosis (75.6%) and Paget's disease (16.5%) were the main indications for treatment; median length of IV BP was 4 years (range 0.25-25). One patient had ONJ (0.5%) while oral pain was reported by 6.5% and 12.7% noted tooth loosening. Twenty-seven subjects (13.4%) complained of current thigh pain. AFF occurred in four patients (2%), none of whom had idiopathic osteoporosis. At time of AFF, only one patient had a femoral neck T-score less than -2.5. All four had received pamidronate treatment; median 12.5 years (range 7-22). IV BP treatment significantly increased lumbar spine BMD but not femoral neck BMD. CONCLUSION: Classical ONJ was rare (0.5%), although tooth loss was more frequent. Thigh pain was frequent while AFF occurred in 2.0% of subjects and was associated with long treatment periods and non-osteoporotic bone.

Don't stop thinking about tomorrow: Individual differences in future self-continuity account for saving.

Some people find it more difficult to delay rewards than others. In three experiments, we tested a "future self-continuity" hypothesis that individual differences in the perception of one's present self as continuous with a future self would be associated with measures of saving in the laboratory and everyday life. Higher future self-continuity (assessed by a novel index) predicted reduced discounting of future rewards in a laboratory task, more matches in adjectival descriptions of present and future selves, and greater lifetime accumulation of financial assets (even after controlling for age and education). In addition to demonstrating the reliability and validity of the future self-continuity index, these findings are consistent with the notion that increased future self-continuity might promote saving for the future.

Bone mineral density of the hip and of the anteroposterior and lateral dimensions of the spine in men with rheumatoid arthritis. Effects of low-dose corticosteroids.

OBJECTIVE: To assess bone mineral density (BMD) in men with steroid-treated rheumatoid arthritis (RA). METHODS: Dual-energy x-ray absorptiometry (DXA) was used to measure BMD in 40 men with RA, 20 of whom were receiving low-dose corticosteroids (< or = 10 mg prednisolone daily), and in 20 healthy, age-matched male controls. RESULTS: BMD was significantly reduced at the femoral neck and greater trochanter in both groups of RA patients, and at the spine from the anteroposterior dimension in the steroid-treated group. CONCLUSION: Low-dose steroid therapy may induce excess axial osteopenia in men with RA.

Clinical features of lupus myositis versus idiopathic myositis: a review of 30 cases.

Myositis is a rare but well-recognized complication of systemic lupus erythematosus (SLE). It is reputed to be milder than primary myositis in terms of morbidity and treatment response. This study compares clinical and laboratory features of idiopathic inflammatory myositis in patients with and without evidence of SLE overlap. We performed a case note review of 30 patients with probable or definite polymyositis/dermatomyositis of whom 11 also had definite or probable SLE. Lupus patients were slightly younger at diagnosis than those with primary disease, and more likely to be female. At presentation, quadriceps strength (expressed as a percentage of expected) was significantly reduced in both the lupus (48.9%; 95% CI 29.0-70.4%) and primary (52.0%; 95% CI 43.6-59.4%) myositis groups, and serum creatine phosphokinase (expressed as a multiple of the upper limit of normal) was significantly elevated (11.2; 95% CI 5.3-29.1 vs 10.7; 95% CI 6.1-17.6). During a mean (S.D.) follow-up period of 7.4 (4.1) yr, both groups tended to follow either a relapsing and remitting, or a chronic persistent course, and when last seen quadriceps muscle strength remained significantly depressed. One of the lupus patients and two of the primary myositis patients died due to direct complications of the disease, and one further death was attributable to a complication of therapy. Our results suggest that lupus myositis is often as severe as primary disease and should be treated with equal vigour.

Anorexia nervosa in a Swedish urban region. A population-based study.

The total population of 15-year-olds in Göteborg, Sweden, were screened in 1985 for anorexia nervosa using brief questionnaires, growth charts and individual school nurse reports. An accumulated frequency of anorexia of 0.84% for girls up to and including 15 years of age was obtained, with 85% of the cases fulfilling DSM-III-R criteria. Boys were affected just over one-tenth as often as girls. The frequency of anorexia nervosa appeared to be much higher in private than in comprehensive schools. The peak age of onset seemed to be 14 years.

Falling and perimenopausal women.

The relationships between falling, fracture and bone density in perimenopausal women have not previously been explored. As part of a population-based screening programme for osteoporosis examining historical risk factors and bone mineral density, we have investigated risk factors for falling in 45-49-year-old women. Our results indicate that the risk of falling may be related to menopausal status, increased body weight, use of diuretics, self-reported arthritis and absence of car ownership.

Pseudosepsis in rheumatoid arthritis due to cellular and lipid abnormalities in synovial fluid.

In acute septic arthritis, the synovial fluid is usually frankly purulent. However, the presence of pus does not always imply the presence of infection, and some synovial fluids are easily mistaken for pus. An exaggeration of the normal leucocyte response in inflammatory joint fluids may alone simulate sepsis; marked increases in certain lipid fractions of the fluid may produce similar appearances. We describe a patient who presented with two examples of such 'pseudoseptic arthritis'.

Systemic lambda light-chain deposition presenting with predominant cardiac involvement.

An 82 year old woman with suspected Bence Jones myeloma developed intractable fluid retention presumed secondary to cardiac failure. In addition she experienced angina pectoris, and required permanent cardiac pacing for symptomatic sinus bradycardia. Postmortem studies revealed prominent myocardial and renal deposits of lambda light-chains which were Congo Red negative, and had a non-fibrillar ultrastructure. Non-amyloidotic light-chain deposition is uncommon, and a rare cause of cardiac disease. Previous work regarding possible pathogenetic mechanisms, clinical and laboratory features and treatment is reviewed.

The effects of alcoholic beverages on urate metabolism in gout sufferers.

The purine contents of commercial, low-alcohol and alcohol-free beers were determined. Four gout sufferers were studied under controlled conditions before and after ingestion of four different beverages containing alcohol, alcohol and purine, purine and neither alcohol nor purine. The results show a significant increase in purine excretion with a fluid load alone and impairment or reversal of this response with the other three beverages. These results are difficult to interpret on the basis of the alcohol and purine contents of the beverages alone. Isohumulones are present in all beers. Their effect on urate metabolism and excretion is unknown but needs further study as a possible explanation of these results. These results suggest that the three beverages other than a fluid load alone are unsuitable for gout sufferers.

Acute myocardial infarction caused by intravenous amphetamine abuse.

A man aged 27 years presented with an acute myocardial infarction after injecting himself intravenously with amphetamine. Soon after admission ventricular fibrillation developed. This was successfully cardioverted. Coronary arteriography was normal.

Recruitment methods for screening programmes: the price of high compliance.

High population compliance is seen as a prerequisite for an equitable screening service. To achieve high compliance fixed appointments are usually advocated. However, the costs of achieving high compliance have not previously been described. To assess the costs of achieving high compliance we have used a randomised trial of two common appointment methods: 800 women aged 45-49 living within 20 miles of Aberdeen were selected at random from the Community Health Index. They were randomly assigned to receive one of two letters--one offering a fixed appointment, the other inviting them to telephone to make an appointment. For a defined population fixed appointments achieved high compliance but only by reducing the opportunities for screening; for every 100 women screened, 110 additional women were denied the opportunity of a screening test. In contrast the open letters of invitation achieved efficiency by increasing the number of women screened with given resources within a larger population. Thus for screening services with fixed budgets, high compliance is achieved only by screening fewer people.