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dc.contributor.advisorReeve, Jonathan
dc.contributor.authorPoole, Kenneth
dc.date.accessioned2013-05-27T08:59:14Z
dc.date.available2013-05-27T08:59:14Z
dc.date.issued2006-02-14
dc.identifier.citation1. Poole KE, Loveridge N, Rose CM, Warburton EA, Reeve J. A Single Infusion of Zoledronate Prevents Bone Loss After Stroke. Stroke 2007; 38:1519-1525. 2. Poole KE, Loveridge N, Barker PJ, Halsall DJ, Rose C, Reeve J, Warburton EA. Reduced vitamin D in acute stroke. Stroke 2006; 37:243-245. 3. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. Faseb J 2005; 19:1842-1844 Poole KE, Reeve J, Warburton EA. Falls, fractures, and osteoporosis after stroke: time to think about protection? Stroke 2002; 33:1432-1436. Poole KE, Kaptoge S, Reeve J. Yearly zoledronic acid in postmenopausal osteoporosis. N Engl J Med 2007; 357:711-712; author reply 714-715. 2. Poole KE, Warburton EA, Reeve J. Risedronate therapy for prevention of hip fracture after stroke in elderly women. Neurology 2005; 65:1513-1514; author reply 1513-1514. 3. Poole KE, Warburton EA, Reeve J. Rapid long-term bone loss following stroke in a man with osteoporosis and atherosclerosis. Osteoporos Int 2005; 16:302-305.en_GB
dc.identifier.otherPhD.29020
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/244611
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/244611
dc.description.abstractStroke is now a well-recognised risk factor for hip fracture. The aim of this study was to elucidate the pathophysiological mechanisms by which hip bone loss occurs in hemiplegia and to test the efficacy of a novel pharmaceutical strategy for preserving bone in stroke patients. Patients who were admitted acutely with a first-ever stroke and who remained unable to walk one week later were studied prospectively for 12 months, with a series of bone mineral density measurements of the hips (dual energy X-ray absorptiometry) in the context of a randomised controlled trial. Untreated patients (n=13) experienced a decline in bone mineral density at the hemiplegic hip that was rapid, with the greatest losses in the trochanteric region of the affected side. This bone loss was prevented by the administration of a single 4 mg dose of the intravenous bisphosphonate, zoledronate (n=14) within 35 days of stroke onset. Computed tomography of the hips in 8 untreated patients more than a year after stroke confirmed that the greatest difference between sides was in the trochanteric region. Serum vitamin D measurements in 44 patients with acute stroke were substantially lower than healthy elderly controls, with 77% of patients in the insufficient range, suggesting that vitamin D insufficiency preceded stroke. Histomorphometric analysis of iliac bone biopsies from hemiplegic patients 10 weeks following stroke showed normal erosion parameters, but a striking decrease in the surface extent of osteoid when compared with healthy reference values. Unexpectedly, treatment with zoledronate was associated with a significantly higher osteoid surface compared with placebo treated subjects in cancellous, endocortical and cortical bone. Sclerostin, a newly discovered osteocyte-derived protein was studied using immunohistochemical staining of the bone biopsies. Sclerostin is known to be an inhibitor of active osteoblasts, which led to the hypothesis that in stroke, the proportion of osteocytes expressing sclerostin would be inversely associated with the surface extent of bone formation. Histological analysis revealed widespread expression of sclerostin in osteocytes and their canaliculi in all subjects. However, examining individual osteocytes in relation to bone forming surfaces revealed that newly embedded osteocytes did not express sclerostin until after primary mineralisation. It is proposed that this precise pattern and timing of sclerostin expression by osteocytes allows bone formation to continue locally (during remodelling), but prevents excessive new bone formation elsewhere, as seen in the single gene disorder sclerosteosis.en_GB
dc.description.sponsorship1. Medical Research Council MRC Clinical Research Training Fellowship RG 35509/ RCAG 057/ G84-6048/LREC 01/245 2. Research Grant National Osteoporosis Society (NOS) Intravenous bisphosphonates in the prevention of osteoporosis associated with stroke. RG 33986/ RCAG 050/ HMW140102/LREC 01/245 3. Raymond and Beverly Sackler PhD Studentshipen_GB
dc.language.isoenen_GB
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectBoneen_GB
dc.subjectOsteoporosisen_GB
dc.subjectOsteocyteen_GB
dc.subjectStrokeen_GB
dc.subjectSclerostinen_GB
dc.subjectHemiplegiaen_GB
dc.subjectComputed tomographyen_GB
dc.subjectHistologyen_GB
dc.subjectImmunohistochemistryen_GB
dc.subjectHistomorphometryen_GB
dc.subjectVitamin Den_GB
dc.titleThe effects of stroke on the skeletonen_GB
dc.title.alternativeSclerostin and the osteocytic control of bone formationen_GB
dc.title.alternativeA Single Injection of Zoledronate Prevents Hip Bone Mineral Density Loss after Strokeen_GB
dc.title.alternativeHypovitaminosis D in Acute Strokeen_GB
dc.title.alternativeStroke and Bone Health; A Histomorphometric Analysisen_GB
dc.typeThesisen_GB
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridgeen_GB
dc.publisher.departmentDepartment of Medicineen_GB
dc.identifier.doi10.17863/CAM.16645


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