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Epidemiological studies have shown an association between bone loss/osteoporosis and vascular calcification (VC). Recent studies have implicated the Wnt signalling pathway in the pathogenesis of VC. We investigated the association between circulating concentrations of Wnt inhibitors; DKK1 and sclerostin with bone mineral density (BMD), abdominal aortic calcification (AAC) and arterial stiffness in post-menopausal women. One hundred and forty six post-menopausal women aged (mean [SD]) 61.5[6.5] years were studied. Sclerostin and DKK1 were measured in serum. BMD was measured at the lumbar spine (LS), femoral neck (FN), total hip (TH). AAC was detected by Vertebral Fracture Assessment (VFA) imaging and quantified using an 8- and 24- point scoring methods. Arterial stiffness was determined by aortic pulse wave velocity (PWV). A significant positive correlation was observed between sclerostin and BMD at the FN (r = 0.166, p = 0.043) and TH (r = 0.165, p = 0.044). The association remained significant at the FN (p = 0.045) and TH (p = 0.026) following adjustment for confounders. No significant correlation was observed between DKK1 and BMD. In contrast, there was a significant negative correlation between log DKK1 and AAC (24-point score: r = -0.25, p = 0.008 and 8-point score: r = -0.21, p = 0.024). Subjects with AAC score of 1 or less had significantly higher DKK1 (p = 0.01). The association between DKK1 and AAC remained significant following correction for age, blood pressure, cholesterol (24-point score: p = 0.017, 8-point score: p = 0.044). In adjusted linear regression analysis, sclerostin was positively associated with AAC (24-point score: p = 0.048, 8-point score: p = 0.031). Subjects with a PWV>9 m/s had significantly higher sclerostin than those with PWV <9 m/s: 23.8[12.3], vs 29.7 [14] pmol/l, p = 0.03). No association was observed between DKK1 and PWV. The opposite association between AAC and the 2 Wnt signaling inhibitors is of interest and merits further investigations. Future longitudinal studies are needed to establish the precise role of sclerostin and DKK1 in the pathogenesis of VC., (Copyright © 2013. Published by Elsevier Inc.)

Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these circumstances changes in bone plasma clearance give a truer impression of response to treatment than those in SUV or uptake., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The functional imaging technique of (18)F-fluoride positron emission tomography ((18)F-PET) allows the non-invasive assessment of regional bone blood perfusion and turnover. Bone perfusion and turnover measured using (18)F-PET correlate closely with those obtained experimentally and so they can be readily applied in clinical research studies. The aim of this study was to compare bone perfusion and turnover between the lumbar spine and humerus in both treatment naïve postmenopausal women (n=11) and those on stable antiresorptive therapy (n=12). All women had a BMD T-score of less than -2 at the spine and/or hip. Each woman had a dynamic PET scan of the lumbar spine and distal humerus after injection of 90 MBq (18)F-fluoride. Using a three-compartmental model bone perfusion (K(1)), the net plasma clearance of tracer to bone mineral (K(i)) reflecting regional bone turnover and the rate constants k(2)-k(4) describing the transport of fluoride between plasma, an extravascular bone compartment and bone mineral compartment were calculated. Mean bone perfusion (K(1)) and bone turnover (K(i)) were significantly higher at the lumbar spine compared to the humerus for both treatment-naïve and antiresorptive groups. K(1) values were on average 3 times greater while K(i) was approximately 50% greater at the lumbar spine. The rate constant k(2), the reverse transport of fluoride from the extravascular compartment to plasma, was significantly lower at the humerus compared to the lumbar spine in both groups. The ratio K(i)/K(1) describing the unidirectional extraction efficiency to bone mineral was significantly greater at the humerus compared to the lumbar spine for both study groups. No significant differences between skeletal sites were observed for k(3) or k(4). In conclusion a significant skeletal heterogeneity was observed in terms of bone perfusion and turnover between the lumbar spine and humerus. (18)F-PET may aid in our understanding of the importance of bone perfusion in osteoporosis and differences in regional bone turnover with disease and in response to therapy.

The clinical attraction of being able to measure bone density in a precise and accurate manner is clear. With this information, clinicians can identify osteopenic postmenopausal women, assess the effects of disease on the skeleton, and examine the effect of therapy. Significant advances have been made in the last decade in methodology of bone-mass measurements, leading to a number of safe, precise, and accurate techniques. The field continues to change and, for example, dual photon absorptiometry, which itself was a major advance, has now effectively been superceded by dual energy X-ray absorptiometry. It is predicted that such methodology will continue to find an expanding role and will soon be considered part of routine clinical practice. A brief review of the various methodologies that have commonly been used for bone-mass measurements is presented.