Role of Vascular Factors in Osteoporosis

Alagiakrishnan, Kannayiram; Juby, Angela; Hanley, David A.; Tymchak, Wayne; Sclater, Anne

doi:10.1093/gerona/58.4.m362

Cited by 94 publications

(76 citation statements)

References 47 publications

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“…The results from this study provided initial evidence that increased bone loss, particularly at the hip, may be a result of decreased vascular support (104). Because of the clinical correlation between vascular calcification and osteoporosis, some authors have suggested that preventive control of vascular risk factors, in addition to standard therapy, would reduce the risk of osteoporotic fracture (105). In a recent study of 103 postmenopausal women, patients with osteoporosis were found to have increased arterial stiffness compared to patients with normal BMD (106).…”

Section: Blood Flow For Maintenance Of Bonementioning

confidence: 69%

Skeletal Blood Flow in Bone Repair and Maintenance

2013

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Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups. IntroductionThe rate at which blood vessels deliver oxygen, nutrients, growth factors, and circulating cells to boneis tightly regulated as a function of blood pressure and vascularizaAll biological tissues, including bone, require vascular support to survive. However, a frequently overlooked feature of bone is its extensive vascular network. Many studies have demonstrated that the blood vessels in bone are necessary for nearly all skeletal functions, including development, homeostasis, and repair (1). In addition, blood vessels lost due to trauma are regenerated, and new bone tissue formed in response to injury is vascularized. As a consequence of this environment, the blood vessels in bone are highly active, not simply a passive source for the delivery of nutrients (2). Readers are referred to recent publications for more information about the active processes of the vasculature not covered in this review, including the vascular niche and hypoxia-driven signaling pathways (3-4). tion. Given that blood pressure is generally maintained, the number and size of blood vessels determines the local blood flow rate. These two factors are regulated through the processes of angiogenesis and vasomotor function, respectively. Although a variety of skeletal disorders are associated with general vascular dysfunction (5-7), this review will focus on the regulation of bone blood flow, through the number and size of vessels, during bone repair and regeneration. To introduce this topic, the skeletal vascular anatomy and techniques for measuring bone blood flow are briefly discussed. Blood supply in boneA dense vascular network delivers oxygen and nutrients to all 206 bones in the human body. In general, this requires a substantial portion of the total cardiac output. Experimental work in various animal species has demonstrated that a significant portion of the resting cardiac output is directed to the skeleton, likely between 10% and 15% (8-12).For some time, the blood flow pattern in bones has been described as primarily centrifugal: blood is supplied to the cortical bone through the nutrient arteries in the (Figure 1), and returned by the periosteal veins (13). Particularly in long bones, the vascular anatomy is well characterized, wi...

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Section: Blood Flow For Maintenance Of Bonementioning

confidence: 69%

Skeletal Blood Flow in Bone Repair and Maintenance

2013

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“…Signals and attractant factors expressed on the bone endothelium help recruit circulating cells, particularly haematopoietic cells to the bone marrow and coordinate with metastatic cells to target them to skeletal regions (Brandi and CollinOsdoby, 2006). Thus, any alteration in the vascular supply to the bone tissue can lead to skeletal pathologies such as osteonecrosis (Childs, 2005); osteomylitis (Lazzerini et al, 2004); and osteoporosis (Burkhardt et al, 1987;Alagiakrishnan et al, 2003). A number of factors have been found to have a prominent effect on the pathology of the vasculature and skeleton, including Osteoprotegerin (OPG), which inhibits Receptor Activator of NF-˜B Ligand (RANKL) induced osteoclastogenic bone resorption (Bucay et al, 1998).…”

Section: Osteogenesis Angiogenesis and Bone Tissue Engineeringmentioning

confidence: 99%

Osteogenesis and angiogenesis: The potential for engineering bone

Kanczler

Oreffo²

2008

eCM

895

637

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The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic) or implants (polymeric or metallic). These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.

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“…Arteries and arterioles within the bone are also subject to arteriosclerosis, and a link between compromised intraosseous circulation and consequent osteoporosis may exist (44). Intraosseous angiogenesis and bone remodeling are regulated by similar cytokines and growth factors, and interactions between bone formation-resorption and blood supply are known to occur (45). A recent study showed that in otherwise healthy women, bone-perfusion indices were lower in women with osteoporosis compared with women with osteopenia or normal BMD (46).…”

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confidence: 99%

Bone–Vascular Axis in Chronic Kidney Disease

London¹

2009

Clinical Journal of the American Society of Nephrology

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C hronic kidney disease (CKD) is characterized by changes in mineral metabolism associated with alterations of its hormonal regulation and various forms of bone disease. In the past, these associations focused attention on the kidney-bone axis. The last decade has seen renewed interest on interactions among mineral metabolism disorders and extraosseous and cardiovascular calcifications observed in CKD or end-stage renal disease (ESRD). Vascular calcification is an active process similar to bone formation that implicates a variety of proteins involved in bone and mineral metabolism (1,2) and is considered part of a systemic dysfunction defined as CKD-mineral and bone disorder (3). Growing evidence linking bone with different functional and structural characteristics of the arterial tree has contributed to developing the concept of the bone-vascular axis (4).The first observations suggesting the existence of the bonevascular axis were the frequent associations of osteoporosis and atherosclerotic vascular calcifications observed in postmenopausal women (5-7). Longitudinal population-based studies revealed a relationship between the progression of vascular calcifications and bone demineralization, and others were identified between bone mineral density (BMD) and aortic or central artery calcifications (6), or coronary arteries in type 2 diabetes (8). The osteopenia-osteoporosis association was also linked with arterial functional indexes, such as aortic stiffness and interactions independent of calcifications, suggesting broader biologic interplay (9,10).Relationships between bone and vascular modifications were also observed in CKD and ESRD patients. In dialysis patients, coronary artery calcification score was found to be inversely correlated with vertebral bone mass (11,12). In addition, a high systemic arterial calcification score combined with bone histomorphometry suggestive of low bone activity was observed in hemodialysis patients (13,14). Arterial stiffening and low spine BMD or calcaneal osteopenia were significantly associated in CKD and hemodialysis patients (15)(16)(17).In the present issue of the Journal, Adragao et al. (18) provide new evidence linking altered bone metabolism to coronary calcifications in patients with stage-5 CKD on hemodialysis. In their cross-sectional study performed on 38 hemodialyzed patients, they analyzed the relationships between bone biopsy parameters (bone volume/total volume, bone formation rate/ bone surface, and activation frequency) and coronary calcifications determined by multislide computer tomography. Their principal conclusion was that low bone volume is associated with more coronary calcifications, whereas histomorphometric parameters of bone turnover were independent of coronary calcifications.Their results complete those of Barreto et al. (12), who found a negative correlation between coronary calcifications and trabecular bone volume or its thickness. The absence of correlations between histomorphometric indexes of bone turnover and coronary calcifications dif...

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Role of Vascular Factors in Osteoporosis

Cited by 94 publications

References 47 publications

Skeletal Blood Flow in Bone Repair and Maintenance

Skeletal Blood Flow in Bone Repair and Maintenance

Osteogenesis and angiogenesis: The potential for engineering bone

Bone–Vascular Axis in Chronic Kidney Disease

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