Reduced Bone Perfusion in Osteoporosis: Likely Causes in an Ovariectomy Rat Model

Griffith, James F.; Wáng, Yì Xiáng J.; Zhou, Hua; Kwong, Wing Hang; Wong, Wing Tak; Sun, Yan; Huang, Yü; Yeung, D.; Qin, Ling; Ahuja, Anil T.

doi:10.1148/radiol.09090608

Cited by 73 publications

(75 citation statements)

References 33 publications

(48 reference statements)

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“…Histologic (14) and radiologic (16-18) studies of osteoporotic bone have shown decreased interosseous blood flow. Ovariectomized rats develop reduced bone marrow blood flow together with reduced bone mineral density and evidence of endothelial dysfunction (19). In people with type 1 diabetes with microvascular complications, serum osteocalcin levels (a protein involved in bone mineralization) are lower than in those people without albuminuria (20,21).…”

Section: Discussionmentioning

confidence: 99%

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures

Barzilay

Gao

Clase

et al. 2013

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures. Design, setting, participants, & measurements This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr). Results There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02). Conclusions Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a theoretical model of a relationship between underlying causes of microalbuminuria and bone disease.

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Section: Discussionmentioning

confidence: 99%

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures

Barzilay

Gao

Clase

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…In this scenario, bone blood flow is significantly decreased while bone turnover is almost totally suppressed. In contrast, the significant increase in bone turnover in ovariectomized rodents has been associated with significant decreases in bone blood flow in a variety of studies using multiple techniques (111)(112)(113)(114). However, this vascular effect has been shown to strongly depend on genetic background (56), potentially explaining controversial reports of increased bone blood flow following rodent ovariectomy by quantifying microspheres (115)(116).…”

Section: Blood Flow For Maintenance Of Bonementioning

confidence: 99%

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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“…Previous investigations have discovered that osteoporosis may lead to decrease in BMSCs' organelles, reduction of BMSCs' viability, differentiation of BMSCs into adipocytes and decreased proliferation of BMSCs in vitro [5,18]. In senile osteoporosis, the molecule that maintains telomerase stability gradually diminishes, causing the telomerase to shorten, thus shortening the BMSCs and osteoblasts' life cycle which results in osteoporosis [19].…”

Section: Discussionmentioning

confidence: 99%

Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells

Zhu

et al. 2012

International Orthopaedics (SICOT)

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Purpose Osteoporosis mainly involves cancellous bone, and the spine and hip, with their relatively high cancellous bone to cortical bone ratio, are severely affected. Studies of bone mesenchymal stem cells (BMSCs) from osteoporotic patients and animal models have revealed that osteoporosis is often associated with reduction of BMSCs' proliferation and osteogenic differentiation. Our aim was to test whether polylactic acidpolyglycolic acid copolymer(PLGA)/collagen type I(CoI) microspheres combined with BMSCs could be used as injectable scaffolds to improve bone quality in osteoporotic female rats. Methods PLGA microspheres were coated with CoI. BMSCs of the third passage and were cultured with PLGA/CoI microspheres for seven days. Forty three-month-old female non-pregnant SD rats were ovariectomized to establish osteoporotic animal models. Three months after being ovariectomized, the osteoporotic rats were randomly divided into five groups: SHAM group, PBS group, cell group, microsphere (MS) group, and cell+MS group. Varying materials were injected into the intertrochanters of each group's rats. Twenty rats were sacrificed at one month and three months post-op, respectively. The femora were harvested in order to measure the intertrochanteric bone mineral density (BMD) with DEXA and trabecular thickness (Tb.Th), percentage of trabecular area (%Tb.Ar), bone volume fraction (BV/TV) and trabecular spacing (Tb.Sp) with Micro CT. One-way ANOVA and Kruskal-Wallis tests were used. Results BMSCs seeded on PLGA/CoI microspheres had a nice adhesion and proliferation. At one month post-op, the BMD (0.33 ± 0.01 g/cm 2 ), Tb.Th (459.65 ± 28.31 μm), %Tb.Ar (9.61±0.29 %) and Tb.Sp (2645.81±94.91 μm) of the cell+MS group were better than those of the SHAM group and the cell group. At three months post-op, the BMD (0.32±0.01 g/cm 2 ), Tb.Th (372.81±38.45 μm), %Tb.Ar (6.65 ± 0.25 %), BV/TV (6.62 ± 0.25 %) and Tb.Sp (1559.03±57.06 μm) of the cell+MS group were also better than those of the SHAM group and the cell group. Conclusion The PLGA/CoI microspheres combined with BMSCs can repair bone defects more quickly. This means that PLGA/CoI microspheres combined with BMSCs can promote trabecular reconstruction and improve bone quality in osteoporotic rats. This scaffold can provide a promising minimally invasive surgical tool for enhancement of bone fracture healing or prevention of fracture occurrence which will in turn minimize complications endemic to patients with osteoporosis.

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Reduced Bone Perfusion in Osteoporosis: Likely Causes in an Ovariectomy Rat Model

Abstract: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090608/-/DC1.

Cited by 73 publications

References 33 publications

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures

Skeletal Blood Flow in Bone Repair and Maintenance

Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells

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