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Matrix metalloproteinase-9 (MMP-9) has been implicated in airways injury in chronic obstructive pulmonary disease (COPD). Osteoporosis is common in patients with COPD, and MMP-9 is an indicator of activated osteoclasts. We hypothesized that circulating MMP-9 would be related to bone mineral density (BMD) in COPD. We explored the relationship between MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1 and -2, and BMD status in patients with COPD. A total of 70 clinically stable patients with confirmed COPD and 39 control subjects underwent spirometry, dual-energy x-ray absorptiometry to determine BMD, and venous sampling for measurement of cytokines and MMP-9 and TIMP-1 and -2. In patients, circulating MMP-9 was increased: mean (SD) 38.5 (2.2) compared with control subjects 20.1 (2.0) ng/mL, P < 0.001, whereas TIMP-1 and -2 were not different. In the patients, MMP-9 was greater in those with osteoporosis, compared with those with osteopenia, no bone disease or control subjects, and patients with osteopenia had greater MMP-9 than control subjects. The adjusted receiver operating characteristics curve area for MMP-9 detecting osteoporosis was 0.86. Patients had elevated systemic inflammatory mediators compared with control subjects, but these were unrelated to bone status. Increased circulating MMP-9 in patients with COPD was related to the presence of osteoporosis and not to lung function. MMP-9 may be a biomarker of increased bone resorption.

Background: Osteoporosis is common in patients with COPD. Previously we have reported that loss of fat-free mass (FFM), measured by dual X-ray absorptiometry (DXA) is associated with loss of bone mineral density (BMD). In addition, in patients with a low body mass index (BMI) and a low FFM, all had evidence of bone thinning, 50% having osteopenia and 50% osteoporosis. We explored the utility of different anthropometric measures in detecting osteoporosis in a community-based COPD population., Methods: Patients with confirmed COPD and not on long-term oral corticosteroids (n=58) performed spirometry. They underwent nutritional assessment by skinfold anthropometry, midarm circumference, calculation of both % ideal body weight (IBW) and BMI. All had DXA assessment of BMD., Results: A total of 58 COPD patients had anthropometric measurements taken, with a mean age of 66.8 (SD 8.7) years, 31 (58%) were male, with a forced expiratory volume in 1s (FEV(1)) of 54.17 (20.18)% predicted. Osteoporosis was present at either the hip or lumbar region in 14 patients (24%). The useful anthropometric measurements identifying those with osteoporosis were both % IBW and BMI. The adjusted odds ratio for %IBW was 0.93 (95% confidence interval (CI) 0.87, 0.99), p=0.016 and for BMI: 0.79 (0.64-0.98), p=0.03. The receiver operating characteristics (ROC) score for both was 0.88, indicating a good fit., Conclusion: Osteoporosis is common, even in patients with mild airways obstruction. Nutritional assessment, incorporating a calculation of their BMI or %IBW may confer an additional benefit in detecting those at risk of osteoporosis and guide referral for BMD measurement.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events and osteoporosis. Increased arterial stiffness is an independent predictor of cardiovascular disease., Objectives: We tested the hypothesis that patients with COPD would have increased arterial stiffness, which would be associated with osteoporosis and systemic inflammation., Methods: We studied 75 clinically stable patients with a range of severity of airway obstruction and 42 healthy smoker or ex-smoker control subjects, free of cardiovascular disease. All subjects underwent spirometry, measurement of aortic pulse wave velocity (PWV) and augmentation index, dual-energy X-ray absorptiometry, and blood sampling for inflammatory mediators., Measurements and Main Results: Mean (SD) aortic PWV was greater in patients, 11.4 (2.7) m/s, than in control subjects, 8.95 (1.7) m/s, p < 0.0001. Inflammatory mediators and augmentation index were also greater in patients. Patients with osteoporosis at the hip had a greater aortic PWV, 13.1 (1.8) m/s, than those without, 11.2 (2.7) m/s, p < 0.05. In patients, aortic PWV was related to age (r = 0.63, p < 0.0001) and log(10) IL-6 (r = 0.31, p < 0.01), and inversely to FEV(1) (r = -0.34, p < 0.01). The strongest predictors of aortic PWV in all subjects were age (p < 0.0001), percent predicted FEV(1) (p < 0.05), mean arterial pressure (p < 0.05), and log(10) IL-6 (p < 0.05)., Conclusions: Increased arterial stiffness was related to the severity of airflow obstruction and may be a factor in the excess risk for cardiovascular disease in COPD. The increased aortic PWV in patients with osteoporosis and the association with systemic inflammation suggest that age-related bone and vascular changes occur prematurely in COPD.

It has been suggested that quantitative ultrasound (QUS) could be used as a selective population pre-screen, to maximise the cost effectiveness of referral for dual energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD). We set out to examine how such an approach might perform in the assessment of women who were referred by general practitioners for DXA via the open access service in Cardiff. In 115 women aged 40-80 (mean 69) years we used DXA to measure BMD at lumbar spine and hip, and QUS to measure broadband ultrasound attenuation (BUA) in the heel. A bottom-up approach was used to estimate the costs of DXA and QUS. We examined the cost effectiveness of using QUS as a pre-screen, only referring subjects for the more expensive DXA assessment if BUA were less than a pre-determined threshold. The unit costs of pencil-beam DXA and QUS were approximately 44 UK pounds and 16 UK pounds respectively. We identified a BUA threshold of 60 dB/MHz as the most cost effective, and calculated a sensitivity of 81% and specificity of 89% in identifying those subjects whom DXA assessment subsequently identified as having osteoporosis. At the BUA threshold of 60 dB/MHz, pre-screening saved 969 UK pounds at the expense of missing ten women with osteoporosis as diagnosed by DXA. Therefore the cost per additional woman with osteoporosis identified using DXA alone was only 97 UK pounds. QUS assessment does not appear to have a significant cost effective benefit as a pre-screen for DXA in the studied population. A QUS pre-screen would be cost effective only if this investigation could be performed at a substantially lower cost.

General practitioners (GPs) are increasingly involved in the selective opportunistic case finding of osteoporosis and treatment of this condition. An open access bone densitometry service has existed for GPs in the Cardiff area since 1993. The purpose of this study was to assess the effectiveness of this service, particularly with respect to the appropriateness of bone densitometry requests and the impact of the service on hospital outpatient referrals. Over a period of 12 months, 560 patients were referred to the open access service by 154 GPs. A total of 229 (41%) patients were given a clinical diagnosis of osteoporosis. Four hundred and seventy-three (84%) referrals followed the clinical referral criteria. In 85% of cases, GPs claimed that they would have referred patients to the hospital outpatient department, if there were no open access bone densitometry service. The majority of the referrals were appropriate, and the service appears to have reduced GP referrals to the specialist clinic.

Objective: To investigate whether vasectomy, which causes immunological and histological changes to the testes and changes to the hypothalamo-pituitary axis, could influence bone mineral density (BMD) and predispose to osteoporosis., Patients and Methods: From patients referred to the Bone Densitometry Clinic, the BMD of L1-L4 and of the hip was analysed in 25 vasectomized men and compared with that in age-matched controls, ensuring that both groups had no secondary causes which might predispose to osteoporosis., Results: In the spine, the mean (standard deviation) BMD was 1.00 (0.19) g/cm2 for the vasectomized men and 0.96 (0.14) g/cm2 for the controls. In the hip (femoral neck and total, respectively) the means were 0.79 g/cm2 and 0.90 g/cm2 for the vasectomized men and 0.72 g/cm2 and 0.96 g/cm2 for the controls. None of the differences were statistically significant., Conclusion: This study does not support the hypothesis that vasectomy may be a risk factor for osteoporosis.

Osteoporotic vertebral fractures result in loss of height and so regular measurement of stature may be a useful method for detecting the onset of the disease and monitoring its progress. The aim of this study was to evaluate the reliability of height measurement in a clinical setting by estimating its precision and the effects of diurnal variation and supine bone densitometry. Duplicate measurements of standing height were made in 50 normal volunteers (25 female) in the morning and 7h later; similar measurements were made in 25 female patients before and after densitometry (spine, one hip and whole body). Portable Harpenden stadiometers were used. The pooled standard deviation (coefficient of variation) ranged from 0.9 mm (0.05%) to 1.7 mm (0.11%). Significant height decrease (> 6 mm) occurred in volunteers during the course of a day while patients showed a significant increase (> 5 mm) after lying supine for an average period of 49 min. Height can be estimated precisely if measurements are made consistently, i.e. using the same equipment and technique, at the same time of day and before bone densitometry. The provision of stadiometers in primary care surgeries and hospital clinics would provide a simple, inexpensive and non-invasive method of assessing the progress of spinal osteoporosis.

Serial measurements of spinal trabecular and radial cortical bone density were made over 4 years in 70 patients with inflammatory bowel disease. Mean rates of bone loss for the cohort differed little from rates reported in normal populations; however, some patients showed increased rates of loss, including patients whose bone density at entry to the study was already well below normal. There was a significant correlation between the amount of corticosteroid prescribed and spinal trabecular bone loss in males, but no significant correlation with other clinical parameters. Increased rates of bone loss emphasise the need for bone densitometry and prophylactic measures in patients with inflammatory bowel disease.

Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.