Dual-energy x-ray absorptiometry scanner mismatch in follow-up bone mineral density testing.

Scanner mismatch occurs frequently with follow-up dual-energy x-ray absorptiometry (DXA) scans. Nearly one-in-five follow-up DXA scans were conducted on non-cross-calibrated scanners (scanner mismatch) and more than a quarter of patients who had a follow-up DXA scan had experienced scanner mismatch. INTRODUCTION: Detecting significant changes in bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) scanners relies on the least significant change (LSC). Results from two different DXA scanners can only be compared, albeit with decreased sensitivity for change, if the LSC between the two scanners has been directly determined through cross-calibration. Performing follow-up DXA scans on non-cross-calibrated scanners (scanner mismatch) has safety and economic implications. This study aims to determine the proportion of scanner mismatch occurring at a population level. METHODS: All patients who completed at least two DXA scans between 1 April 2009 and 31 December 2018 in the province of Alberta, Canada, were identified using population-based health services databases. Scanner mismatch was defined as a follow-up DXA scan completed on a DXA scanner that differed from and was not cross-calibrated to the previous DXA scanner. Multivariate logistic regression models were used to assess predictive factors that may contribute to scanner mismatch. RESULTS: A total of 264,866 patients with 470,641 follow-up DXA scans were identified. Scanner mismatch occurred in 18.9% of follow-up DXA scans; 28.7% of patients experienced at least one scanner mismatch. Longer duration between scans (OR 1.25, 95% CI 1.24-1.26) and major osteoporotic fracture history before index scan (OR 1.06, 95% CI 1.03-1.08) increased risk of scanner mismatch. Osteoporosis medication use before index scan (OR 0.89; 95% CI 0.88-0.91), recency of follow-up scans (OR 0.98, 95% CI 0.73-0.98), female sex (OR 0.97, 95% CI 0.94-1.00), and age at last scan (OR 0.99, 95% CI 0.99-1.00) were associated with lower risk of scanner mismatch. CONCLUSION: Scanner mismatch is a common problem, occurring in one-in-five follow-up DXA scans and affecting more than a quarter of patients. Interventions to reduce this large proportion of scanner mismatch are necessary.

Vitamin D status and risk for sarcopenia in youth with inflammatory bowel diseases.

Suboptimal vitamin D (vitD) status and reduced lean body mass are highly prevalent in pediatric inflammatory bowel diseases (IBD). The study objective was to determine sarcopenia prevalence and associations with vitD status in newly diagnosed pediatric IBD. Children with Crohn's disease (CD; n = 58) and ulcerative colitis (UC; n = 27) were included. Primary outcomes included body composition (total/regional/percent fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM)), and vitD status (serum 25(OH)D). Sarcopenia was defined as SMM-z < -2. Additional variables measured included serum CRP, ESR, anthropometric, Pediatric Crohn's Disease Activity Index (PCDAI), and the Pediatric Ulcerative Colitis Disease Activity index (PUCAI). Sarcopenia and suboptimal 25(OH)D levels (< 50 nmol/l) were found in 23.5% (n = 20) and 52% (n = 44) of children, respectively. Younger children (< 13 years) with CD with suboptimal 25(OH)vitD (< 50 nmol/l) had the greatest frequency of sarcopenia (57.1%) (p = 0.004). Sarcopenia was prevalent in newly diagnosed, young children with CD with vitD deficiency.

Women with severe obesity and relatively low bone mineral density have increased fracture risk.

UNLABELLED: Among women with obesity, those with the lowest bone density have the highest fracture risk. The types of fractures include any fracture, fragility-type fractures (vertebra, hip, upper arm, forearm, and lower leg), hand and foot fractures, osteoporotic, and other fracture types. INTRODUCTION: Recent reports have contradicted the traditional view that obesity is protective against fracture. In this study, we have evaluated the relationship between fracture history and bone mineral density (BMD) in subjects with obesity. METHODS: Fracture risk was assessed in 400 obese women in relation to body mass index (BMI), BMD, and clinical and laboratory variables. RESULTS: Subjects (mean age, 43.8 years; SD, 11.1 years) had a mean BMI of 46.0 kg/m(2) (SD, 7.4 kg/m(2)). There were a total of 178 self-reported fractures in 87 individuals (21.8% of subjects); fragility-type fractures (hip, vertebra, proximal humerus, distal forearm, and ankle/lower leg) were present in 58 (14.5%). There were higher proportions of women in the lowest femoral neck BMD quintile who had any fracture history (41.3 vs. 17.2%, p < 0.0001), any fragility-type fractures (26.7 vs. 11.7%, p = 0.0009), hand and foot fractures (16.0 vs. 5.5%, p = 0.002), other fracture types (5.3 vs. 1.2%, p = 0.02), and osteoporotic fractures (8.0 vs. 1.2%, p < 0.0001) compared to the remaining population. The odds ratio for any fracture was 0.63 (95% CI, 0.49-0.89; p = 0.0003) per SD increase in BMD and was 4.3 (95% CI, 1.9-9.4; p = 0.003) in the lowest BMD quintile compared to the highest quintile. No clinical or biochemical predictors of fracture risk were identified apart from BMD. CONCLUSIONS: Women with obesity who have the lowest BMD values, despite these being almost normal, have an elevated risk of fracture compared to those with higher BMD.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.

UNLABELLED: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

The development of bone mineral lateralization in the arms.

UNLABELLED: Bone mineral content (BMC) is known to be greater in the dominant arm after the age of 8 years. We studied a group of children and found that BMC sidedness gradually increased up to the age of 6 years and then remained stable into late adolescence. INTRODUCTION: Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. METHODS: Subjects (N = 158) were children recently initiating glucocorticoids for underlying disease (leukemia 43 %, rheumatic conditions 39 %, nephrotic syndrome 18 %). Handedness was determined by questionnaire and BMC by dual-energy X-ray absorptiometry. RESULTS: Median age was 7.2 years (range, 1.5 to 17.0 years), 49 % was male, and the spine BMD Z-score was -0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95 % CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). CONCLUSIONS: These results show that arm BMC sidedness in this patient group develops up to age 6 years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines.

SUMMARY: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine. INTRODUCTION: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults. METHODS: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures). RESULTS: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years. CONCLUSIONS: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome.

SUMMARY: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). INTRODUCTION: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. METHODS: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. RESULTS: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. CONCLUSIONS: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

The accuracy of clinical kyphosis examination for detection of thoracic vertebral fractures: comparison of direct and indirect kyphosis measures.

OBJECTIVE: To compare the accuracies of two simple physical examination maneuvers for detecting the presence of thoracic vertebral fractures (VF) diagnosed by radiography: direct measurement of kyphosis angle (KA, in degrees) and indirect measurement using wall-occiput distance (WOD, in cm). METHODS: Subjects were 280 women (average age, 54.5 years; range, 18-92) referred for assessment of osteoporosis. KA was measured from T4 to T12 using a digital inclinometer while WOD was measured with the patient in a standardized position. VF were diagnosed on radiographs using semi-quantitative morphometry. RESULTS: KA and WOD were moderately correlated (r = 0.72, p<10(-11)). KA increased by 3.7(o) (95% CI, 2.6-4.8(o)) for each VF (p = 4x 10(-11)) and WOD rose 1.3 cm (95% CI, 0.8-1.7 cm) per VF (p = 2 x 10(-11)). The areas under the receiver operating characteristic curves were 0.72 (95% CI, 0.65-0.79) for KA and 0.76 (95% CI, 0.69-0.82) for WOD, which were not significantly different (p = 0.13). CONCLUSIONS: Given similar performances of direct and indirect measures of kyphosis, we propose that WOD should be used in clinical practice, with a clinical threshold of WOD>4.0 cm as an indication to consider spine radiography. At this WOD threshold, sensitivity was 41% (95% CI, 31-52%) and specificity was 92% (95% CI, 87-95%). WOD should be considered for use in the clinical assessment of osteoporosis patients.

Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders.

OBJECTIVE: Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. METHODS: Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. RESULTS: Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004). CONCLUSION: In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

Population-based Canadian hip fracture rates with international comparisons.

SUMMARY: We identified hospitalizations throughout Canada during 2000-2005 in which the most responsible diagnosis was a proximal femoral fracture. Use of the US fracture risk assessment tool (FRAX) would be inappropriate for Canada as it would overestimate fracture risk in Canadian women and older men. INTRODUCTION: It is recommended that the WHO fracture risk assessment tool should be calibrated to the target population. METHODS: We identified hospitalizations for women and men throughout Canada during the study period 2000-2005 in which the most responsible diagnosis was a proximal femoral fracture (147,982 hip fractures). Age-standardized hip fracture rates were compared between Canadian provinces, and national rates were compared with those reported for the USA and Germany. RESULTS: There were relatively small differences in hip fracture rates between provinces, and most did not differ appreciably from the Canadian average. Hip fracture rates for women in Canada in 2001 were substantially lower than in the USA (population-weighted rate ratio 0.70) and were also lower than in Germany for 2004 (population-weighted rate ratio 0.74). CONCLUSIONS: Overall hip fracture rates for Canadian women were found to be substantially lower than those for the USA and Germany. This study underscores the importance of assessing country-specific fracture patterns prior to adopting an existing FRAX tool.

Risk factors for low BMD in healthy men age 50 years or older: a systematic review.

SUMMARY: In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications. INTRODUCTION: Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older. MATERIALS AND METHODS: A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria. RESULTS: Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss. CONCLUSION: In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice.

Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature.

UNLABELLED: Based on a systematic review of the literature, only low body weight and menopausal status can be considered with confidence, as important risk factors for low BMD in healthy 40-60 year old women. The use of body weight to identify high risk women may reduce unnecessary BMD testing in this age group. INTRODUCTION: BMD testing of perimenopausal women is increasing but may be unnecessary as fracture risk is low. Appropriate assessment among younger women requires identification of risk factors for low BMD specific to this population. METHODS: We conducted a systematic literature review of risk factors for low BMD in healthy women aged 40-60 years. Articles were retrieved from six databases and reviewed for eligibility and methodological quality. A grade for overall strength of evidence for each risk factor was assigned. RESULTS: There was good evidence that low body weight and post-menopausal status are risk factors for low BMD. There was good or fair evidence that alcohol and caffeine intake, and reproductive history are not risk factors. There was inconsistent or insufficient evidence for the effect of calcium intake, physical activity, smoking, age at menarche, history of amenorrhea, family history of OP, race and current age on BMD. CONCLUSIONS: Based on current evidence in Caucasians, we suggest that, in healthy women aged 40-60 years, only those with a low body weight (< 70 kg) be selected for BMD testing. Further research is necessary to determine optimal race-specific discriminatory weight cut-offs and to evaluate the risk factors for which there was inconclusive evidence.

The accuracy of historical height loss for the detection of vertebral fractures in postmenopausal women.

Historical height loss (HHL) can be calculated as the difference between a patient's tallest recalled height (TRH) and the current measured height (MH). We have examined the accuracy of HHL as a clinical test for the detection of prevalent vertebral fractures. Subjects were postmenopausal women aged 50 or older who had been referred for specialist assessment of osteoporosis risk (n=323; average age 66.0+/-9.2 years; range 50-92 years). MH was determined using a wall-mounted stadiometer. The presence of prevalent vertebral fractures was assessed by radiographic morphometry, with fracture defined as a vertebral height ratio<0.8. The positive likelihood ratio (LR+) for fracture was relatively flat until HHL>6.0 cm. With HHL from 6.1 to 8.0 cm, the LR+ was 2.8 [95% confidence interval (95%CI), 1.3, 6.0]. When HHL was >8.0 cm, the LR+ was 9.8 (95% CI, 3.0, 31.8). The area under the receiver operating characteristics curve for the ability of HHL to detect fracture was 0.66 (95% CI, 0.59, 0.72). At HHL>6.0 cm, sensitivity was 30% (95% CI, 22, 37%), and specificity was 94% (95% CI, 90, 97%). The positive predictive value was relatively low across a range of theoretical prevalence, rising above 80% only at very high prevalence rates (>50%). In contrast, the negative predictive value was high at the prevalence rates seen in most clinical practice, and dropped below 80% only when the prevalence exceeded 25%. This study shows that HHL6.0 cm should have spine radiographs to examine for the presence of vertebral fractures.

A simple method for determining the probability a new vertebral fracture is present in postmenopausal women with osteoporosis.

The vertebral fracture status of women with osteoporosis has strong prognostic implications that may influence clinical decisions. We developed a simple method for estimating the probability that a new vertebral fracture has occurred in postmenopausal women with osteoporosis. Data was from the placebo groups of the Fracture Prevention Trial (median observation =21 months) and the MORE Trial at 2 years. A logistic regression analysis identified prior vertebral fracture (yes/no), new or worsening back pain (yes/no), and height loss (> or =2 cm, yes/no) as significant predictors for the presence of a new vertebral fracture. The actual probability of a new vertebral fracture in patients without these predictors, over the median observation period of 23 months, was 2.1%. Presence of back pain increased this probability fourfold; prior vertebral fracture increased this probability threefold, and height loss > or =2 cm increased this probability threefold. The predicted probabilities of a new vertebral fracture being present for each subgroup representing each of the eight possible combinations of back pain, prior vertebral fracture, and height loss were highly correlated with both the multivariate logistic regression-derived probabilities (r=0.98, p <0.001) and with the actual probabilities (r=0.99, p <0.001). The validity of this simple method was confirmed in patients from the MORE trial at both 2 years and 3 years, and in the Fracture Prevention Trial alone. This simple method provides clinicians with an estimate of the probability that a new vertebral fracture has occurred in postmenopausal women with osteoporosis.

Accuracy of height loss during prospective monitoring for detection of incident vertebral fractures.

Vertebral fractures are the most common type of osteoporotic fracture, but more than two-thirds remain undetected. We have examined the relationship between height loss and the development of new vertebral fractures to determine whether there is a height loss threshold that has useful clinical accuracy to detect new fractures. We studied 985 postmenopausal women with osteoporosis in the placebo arms of the Vertebral Efficacy with Risedronate Therapy studies. Height was measured annually for 3 years using a wall-mounted stadiometer. New fractures were determined using quantitative and semi-quantitative radiographic morphometry. The relationship between height loss over three years and the number of new vertebral fractures was: height loss (cm) = 0.95 x number of new vertebral fractures-0.4 cm (r = 0.33). The odds ratio for the development of a new fracture increased up to 20.6 (95% confidence interval, 9.3, 45.8) when height loss was greater than 4.0 cm. At a threshold of > 2.0 cm height loss over 3 years, sensitivity was 35.5% for detecting new vertebral fractures and specificity was 93.6%. These findings show that there is a strong relationship between the amount of height loss and the risk of a new vertebral fracture. While there is no cut-off that can reliably rule in a new fracture, height loss of < or = 2.0 cm over 1-3 years has acceptable accuracy for ruling out an incident fracture.

Underreporting of vertebral fractures on routine chest radiography.

OBJECTIVE: Osteoporosis is underdiagnosed and therefore undertreated. We determined the potential usefulness of chest radiography for detecting clinically important vertebral fractures by performing semiquantitative reviews and quantitative digital morphometry on 100 routine chest radiographs taken in the emergency department and comparing the yield of these independent reviews with official radiology reports. MATERIALS AND METHODS: One hundred randomly selected chest radiographs of patients 60 years or older who presented to the emergency department of a tertiary care hospital were evaluated. Radiographs were selected without knowledge of the presenting complaint and were independently reviewed by two board-certified radiologists and a radiology resident. A validated semiquantitative method was used to assess lateral chest radiographs for vertebral fracture. In addition, quantitative digital morphometry was undertaken. A clinically important vertebral fracture was defined as one that was at least moderate to severe (loss of height >or=> 25%). RESULTS: Mean age of the population was 75 years, 47% were women, and 46% were admitted to the hospital. According to the reference radiologist, prevalence of moderate to severe vertebral fractures was 22%. Simple agreement was 87-88% among reviewers; kappa values were moderate (0.56-0.58). The greatest agreement was between the reference standard radiologist and quantitative digital morphometry (89% agreement; kappa = 0.67). Only 55% (12/22) of vertebral fractures we identified were mentioned in the official radiology reports. CONCLUSION: Chest radiography has potential as a screening tool for revealing previously undiagnosed vertebral fractures, although in this study only half of moderate to severe fractures that we identified were mentioned in official reports.

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Intravenous pamidronate for treatment of reflex sympathetic dystrophy during breast feeding.

A 39-year-old woman presented in the first month of pregnancy with reflex sympathetic dystrophy involving both lower legs. Symptoms became so severe that she could not walk unassisted, and the pain worsened after delivery. Radiographs showed patchy reduction in apparent density in the tarsal bones and around the ankles and knees. Uptake was increased in these areas on technetium methylene diphosphonate bone scan. Bone density (dual-energy X-ray absorptiometry) was reduced in the spine, hip, and radius. Biochemical tests were normal except for an increase in urinary excretion of the N-telopeptide cross-linking region of type I collagen (NTx). Because the patient wanted to continue breast-feeding, intravenous pamidronate was administered at monthly intervals. Breast milk was collected for 48 h after the infusion. The pain began to decrease soon after drug administration was initiated, and it was virtually gone by 6 months. NTx excretion fell by 78% and bone density increased by as much as 18.9% over the 6-month treatment interval. The baby was healthy and grew normally. Milk expressed after the first treatment was assayed for pamidronate content by high-performance liquid chromatography with fluorescence detection. None was detected (limit of quantitation, 0.4 micromol/liter). This case shows that pamidronate may be considered for treatment of lactating women.