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Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O2, nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to influencing bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered. [ABSTRACT FROM AUTHOR]

It has previously been demonstrated that impaired angiogenesis is associated with metabolic abnormalities in bone in addition to osteoporosis (including postmenopausal osteoporosis). Enhancing vessel formation in bone is therefore a potential clinical therapy for osteoporosis. The present study conducted an in‑depth investigation using desferrioxamine (DFO) in an ovariectomy (OVX)‑induced osteoporotic mouse model in order to determine the time frame of alteration of bone characteristics and the therapeutic effect of DFO. It was demonstrated that OVX induced instant bone mass loss 1 week following surgery, as expected. In contrast, DFO treatment protected the mice against OVX‑induced osteoporosis during the first week, however failed to achieve long‑term protection at a later stage. A parallel alteration for cluster of differentiation 31/endomucin double positive vessels (type H vessels) was observed, which have previously been reported to be associated with osteogenesis. DFO administration not only partially prevented bone loss and maintained trabecular bone microarchitecture, however additionally enhanced the type H vessels during the first week post‑OVX. The molecular mechanism of how DFO influences type H vessels to regulate bone metabolism needs to be further investigated. However, the findings of the present study provide preliminary evidence to support combined vascular and osseous therapies for osteoporotic patients. Pharmacotherapy may offer a novel target for improving osteoporosis by promoting type H vessel formation, which indicates potential clinical significance in the field of bone metabolism. [ABSTRACT FROM AUTHOR]

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The discoid lateral meniscus (DLM) is an anatomically abnormal meniscus that covers a greater area of the tibial plateau than the normal meniscus. The DLM is classified into two types: complete (CDLM) and incomplete (ICDLM) types. In this study, we investigated the histological and cell biological characteristics of CDLM and ICDLM. The number of blood vessels, proteoglycan deposition, and collagen distribution were assessed using meniscal tissues. Collagen production was also investigated in CDLM and ICDLM cells.The intercondylar region of the CDLM had a higher number of blood vessels than the inner region of the ICDLM. Safranin O staining density and type II collagen deposition in ICDLM were higher than those in CDLM. Type II collagen-positive cells were higher in ICLDM than in CDLM. CDLM cells showed slender fibroblastic morphology, while ICDLM cells were triangular chondrocytic in shape. This study demonstrated that the intercondylar region of the CDLM showed similar properties to the outer region of the meniscus. The inner region of the ICDLM, on the other hand, differed from the intercondylar region of the CDLM. Our results suggest that the intercondylar region of the CDLM may have a high healing potential like the outer meniscus. [ABSTRACT FROM AUTHOR]

Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016) of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases. [ABSTRACT FROM AUTHOR]

Purpose: In this study, magnetic resonance angiography (MRA) was performed in the early phase after anterior cruciate ligament (ACL) reconstruction to analyse the changes in nutrient blood vessels and blood flow to the femoral and tibial tunnels and the intraosseous tendon grafts.Methods: The subjects were 30 patients who underwent single-bundle ACL reconstruction with an autogenous hamstring tendon. MRA was performed at 2, 3, and 6 months postoperatively (n = 10 at each time point). The mean overall signal-to-noise ratios (SNRs) in the tunnel regions and in the region of the tendon graft were compared in each femur and tibia.Results: Blood vessels from arteries reached the femoral and tibial tunnels 2 months postoperatively. The tunnel walls showed high signal intensity, while the intraosseous tendon grafts had lower intensity. SNRs showed significant differences between the femoral and tibial tunnels overall and the intraosseous tendon grafts. At 3 and 6 months postoperatively, the signal intensity of the tunnel walls was decreased significantly, while that of the intraosseous tendon grafts was also decreased, but not significantly. At these times, the SNRs of the femoral and tibial tunnels did not differ significantly, both overall and in the region of the intraosseous tendon grafts.Conclusion: Revascularization around the femoral and tibial tunnels occurred at 2 months postoperatively, with blood flow subsequently decreasing over time until 6 months. This revascularization may be involved in bone tendon healing and maturation of the tendon graft within the bone tunnels. Evaluations of revascularization by MRA may show the maturation stage of the graft and guide medical rehabilitation.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

The study of bone blood flow regulation in humans has always represented a difficult task for the clinician and the researcher. Classical measurement techniques imply the presence of ionizing radiation or contrast agents, or they are slow or cannot be repeated too often in time. In the present review, we would like to give a perspective on how the optical approach might overcome some of these problems and give unique solutions to the study of bone blood flow regulation. We hope that the present contribution will encourage the scientific community to put a greater attention on this approach. [ABSTRACT FROM AUTHOR]

The pathophysiology of Kienböck's disease is not well understood: factors that were previously considered as potentially being responsible for the disease are now only seen as predisposing factors that contribute to discovering pre-existing disease. The natural history of the disease is also not well known. The arthroscopic classification proposed by Bain and Begg is now an essential supplement to the well-known Lichtman radiographic classification system. Various treatment options exist and some are better suited to each stage of the disease. This review will explore the advantages and disadvantages of these treatment options and match them with the best indications. [ABSTRACT FROM AUTHOR]

Abstract: Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6month; n=8) and old (22–24month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p <0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p <0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in “microvascular dead space” in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. [Copyright &y& Elsevier]

Abstract: The induced membrane has been widely used in the treatment of large bone defects but continues to be limited by a relatively lengthy healing process and a requisite two stage surgical procedure. Here we report the development and characterization of a synthetic biomimetic induced membrane (BIM) consisting of an inner highly pre-vascularized cell sheet and an outer osteogenic layer using cell sheet engineering. The pre-vascularized inner layer was formed by seeding human umbilical vein endothelial cells (HUVECs) on a cell sheet comprised of a layer of undifferentiated human bone marrow-derived mesenchymal stem cells (hMSCs). The outer osteogenic layer was formed by inducing osteogenic differentiation of hMSCs. In vitro results indicated that the undifferentiated hMSC cell sheet facilitated the alignment of HUVECs and significantly promoted the formation of vascular-like networks. Furthermore, seeded HUVECs rearranged the extracellular matrix produced by hMSC sheet. After subcutaneous implantation, the composite constructs showed rapid vascularization and anastomosis with the host vascular system, forming functional blood vessels in vivo. Osteogenic potential of the BIM was evidenced by immunohistochemistry staining of osteocalcin, tartrate-resistant acid phosphatase (TRAP) staining, and alizarin red staining. In summary, the synthetic BIM showed rapid vascularization, significant anastomoses, and osteogenic potential in vivo. This synthetic BIM has the potential for treatment of large bone defects in the absence of infection. [Copyright &y& Elsevier]

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphy-sis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers. [ABSTRACT FROM AUTHOR]

Objectives Restoration of an adequate blood supply is essential for the bone healing process and is key to the success of bone augmentation procedures. In this study, we evaluated angiogenesis in rat calvarial flat bone defects using in vivo microfocus computed tomography (micro- CT). Materials and methods Twenty rats were used. The calvarium was exposed and calvarial bone defects of critical (5-mm diameter) and non-critical (2.7-mm diameter) sizes were prepared. Bone regeneration and angiogenesis were evaluated by image analysis using micro- CT and histological examination. Results Critical- and non-critical-sized calvarial bone defects showed bone regeneration and angiogenesis around the midsagittal suture. Critical-sized calvarial bone defects showed approximately 1.2% reossification of the original surgical defect, whereas the non-critical-sized defects showed approximately 43.3% reossification at day 28. Furthermore, angiogenesis was observed later in the critical-sized calvarial bone defects (about 38.2%), whereas angiogenesis was observed early in the non-critical-sized calvarial bone defects (about 75.5%) at day 28. New blood vessel networks were observed around defects of both sizes. Conclusions Angiogenesis preceded bone regeneration around critical- and non-critical-sized calvarial bone defects. Angiogenesis led to full bone formation in non-critical-sized defects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intermittent PTH administration directly stimulates osteoblasts; however, mechanisms of bone accrual that are independent of the direct actions on osteoblasts may be under-appreciated. Our aims were to decipher (1) whether PTH 1-84 augments vasodilation of the femoral principal nutrient artery (PNA), (2) whether 15days of intermittent PTH 1-84 augments endothelium-dependent and/or -independent vasodilation of the femoral PNA, and (3) the signaling mechanisms involved. Methods: Experiment 1: Femoral PNAs from male Wistar rats were exposed to cumulative doses of PTH 1-84 with and without an anti-vascular endothelial growth factor antibody and/or the endothelial NO synthase inhibitor l-NAME. Experiment 2: Male Wistar rats were administered PTH and/or the anti-VEGF antibody for 2weeks. Subsequently, endothelium-dependent vasodilation to acetylcholine and endothelium-independent vasodilation to sodium nitroprusside were assessed. In addition, endothelium-dependent signaling pathways were analyzed by use of l-NAME and/or and the cyclooxygenase inhibitor indomethacin. Results: Cumulative doses of PTH 1-84 induced vasodilation of the femoral PNA, which was reduced by 38% and 87% with the anti-VEGF antibody and l-NAME, respectively. Secondly, 2weeks of intermittent PTH 1-84 administration doubled trabecular bone volume, augmented bone formation parameters and reduced osteoclast activity. In addition, PTH enhanced endothelium-dependent vasodilation via up-regulation of NO. Co-administration of the anti-VEGF antibody (1) inhibited the PTH-induced increase in bone volume and remodeling parameters and (2) blunted the augmented vasodilator responsiveness of the PNA. Finally, endothelium-dependent vasodilation in PTH-treated rats was highly correlated with trabecular bone volume. Conclusion: As hypothesized, PTH enhanced endothelium-dependent vasodilation of the femoral PNA via augmented NO production and was mediated partially through VEGF signaling. Further, vasodilation to PTH appears independent of vascular smooth muscle cell participation. More importantly, the strong association between vasodilation and bone volume suggests that bone arteriolar function is critical for PTH-induced bone anabolism. [Copyright &y& Elsevier]

Abstract: Previously, to create an implantable bone tissue associated with blood vessels, we co-cultured rabbit bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial cells (ECs) within a porous polylactic acid-based scaffold utilizing a rotating wall vessel (RWV) bioreactor. Here, this engineered tissue was orthotopically implanted into defects made in femurs of immunodeficient rats, and histological analysis were carried out to examine the repair of the damage and the formation of bone around the implant. The bone defects were better repaired in the implanted group than control group after 3 weeks. The results indicate that the engineered bone could repair bone defects. [Copyright &y& Elsevier]

Hyaluronic acid (HA) and fibrin glue (FG) are effective hydrogels for tissue engineering applications as they support tissue in-growth, retain growth factors, and release them slowly with time. The scaffolds, in combination with a hydrogel, effectuate a successful graft. However, the survival of a graft entirely depends upon a functional vascular supply. Therefore, hydrogels must support the in-growing vasculature. To study and compare the vascular patterns, HA and FG hydrogel-containing PLDLLA-TCP-PCL scaffolds were implanted in the groin of male Lewis rats and supplied with a micro-surgically prepared arterio-venous (A-V) loop. The rats were perfused with a vascular contrast media after 4 and 8 weeks and sacrificed for further analysis. The specimens were scanned with micro-CT to find the vascular growth patterns. Corrosion casting of blood vessels followed by SEM demonstrated a high vascular density near the parent blood vessels. Histologically, HA and FG implanted animal groups showed significant angiogenetic activity, especially within the pores of the scaffold. However, formation of new blood vessels was more conspicuously observed at 4 weeks in FG than HA implants. Furthermore, by 8 weeks, the number and pattern of blood vessels were comparable between them. At this time, HA was still present indicating its slow degradation. The finding was confirmed by histomorphometric analysis. This experimental study demonstrates that HA containing composite scaffold systems permit stabile in-growth of blood vessels due to sustained degradation over 8 weeks. HA is a potential matrix for a tissue engineered composite graft. [ABSTRACT FROM PUBLISHER]

Variations in the origin of axillary artery branches are common. But, distinctly abnormal course of its posterior circumflex humeral branch is rare. We are reporting a case of posterior circumflex humeral artery (PCHA) originating from the axillary artery, passing through lower triangular space to reach the scapular region where it accompanied the axillary nerve and posterior circumflex humeral vein to pass around surgical neck of humerus, deep to the fibers of deltoid. Other variations observed in this specimen were the radial collateral artery arising from the PCHA, middle collateral artery arising directly from the brachial artery and absence of profunda brachii artery. PCHA forming a hair pin loop, traversing through lower triangular space instead of quadrangular space taking a long course is being reported for the first time. Further, the clinical and surgical importance of this case especially in relation with quadrangular space syndrome and relevant literature is discussed. [ABSTRACT FROM AUTHOR]

Background: Photothrombosis was introduced as a model of ischemic stroke by Watson et al. in 1985. In the present paper, we describe a protocol to induce photothrombotic infarcts in rats. Findings: The photosensitive dye Bengal Rose is intravenously administered and a laser beam is stereotactically positioned onto the skull. Illumination through the intact skull leads to local activation of Bengal Rose, which results in free radical formation, disturbance of endothelial function and thrombus formation in illuminated small cortical vessels. Conclusions: Photochemically induced infarcts cause long-term sensorimotor deficits, allow long-term survival and are particularly suitable to assess the effectiveness of neuroregenerative therapies in chronic stroke studies. [ABSTRACT FROM AUTHOR]

Objective: The first objective of this study was to find out the weakest part of the hook of the hamate, the second objective was to find out the vascular pattern of the weakest part. Materials and Methods: We used 55 dry bones from the Department of Anatomy, Manipal University. Bones were from adult cadavers of South Indian origin. Among 55 bones, 27 were from the right side and 28 from the left side. We measured morphometric parameters using a Metal Casing Electronic Digital Caliper, resolution 10µm. A magnifying lens (magnifying power 10x) was used to visualize the vascular foramina. Results: The differences between the right and the left hamate hooks were not statistically significant for any of the variables. (P>0.05). All hamate hooks had vascular foramina at their bases. In 17 (30%) bones, no vascular foramina were seen at the tip of the bone. Only four hamate hooks had vascular foramina at the bend. Conclusion: From the present study, we hypothesize that the bend of the hamate hook could be its weakest part, and since most of the hamate hooks lack vascular foramina at the bend, this site could be more prone to avascular necrosis. The study also aids to establish data on the hamate hook in a South Indian population. ( [ABSTRACT FROM AUTHOR]

Purpose: Osteocutaneous free flaps (OFF) are widely used to reconstruct large bone defects in trauma and cancer surgery. Currently no monitoring method is available to detect blood circulation around and inside the bone after transplantation. Therefore we used for the first time contrast-enhanced high-resolution ultrasound (hrCEUS) to gain evidence for the microcirculation of the transplanted bone. Materials and methods: 15 patients transplanted with OFF because of large bone defects at different sites were examined postoperatively with hrCEUS with a high resolution linear probe (6-9 MHz, LOGIQ E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue®, Bracco, Italy). Operation and examination were performed by either an experienced plastic surgeon or an experienced ultrasound examiner. Microcirculation of the periost and bone was analyzed in different regions of interest (ROIs) and quantitative microcirculation analysis was performed using time intension curve analysis (TIC). We further analyzed clinical outcome of the patients in respect to revision-surgery, necrosis of the OFF and flap survival as well as viability on standard x-rays 2 months after surgery. Results: The most representative parameter by TIC analysis of hrCEUS were the area under the curve (AUC) and the time to peak (Ttop). The AUC of the periost and central part of the bone showed a high correlation (Pearson's r = 0.831). Mean AUC for the periost was 163.92 dB ± 49.44 and for the central part of the bone 70.42 dB ± 25.33. The Ttop of the periosteal ROI was 33.04 sec. ± 6.71 and the bone ROI 41.01 sec. ± 9.24. There was a high correlation of the Ttop of the periost and bone (Pearson's r = 0.937). One revision had to be performed due to haematoma and microcirculation defect of the distal part of the transplanted bone graft which was detected early by hrCEUS and the distal part of the avital bone could be removed timely. Conclusion: For the first time we could show that hrCEUS is a reliable method to evaluate the viability of OFF. The AUC and Ttop seem to be a valuable parameter to detect the microcirculation around and inside the bone transplant. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intraosseous arteriovenous malformations (AVMs) in the maxillofacial area are rarely reported in the current literature. These malformations have been associated with severe hemorrhage resulting in significant morbidity and mortality. The recommended gold standard treatment of AVMs is an endovascular embolization, combined with surgery. Especially in children, disease management remains a challenge for the surgeon due to the process of bone growth. Aim: In this report, we describe our experience with a microvascular bone graft as another possible surgical technique for the treatment of intraosseous AVMs in children. Patient and methods: A 15-year-old boy was admitted to our department with a life-threatening hemorrhage due to an AVM of the left mandible. The attempt of an ordinary tooth extraction had lead to the emergency. Several embolizations and surgical interventions were required. Finally, a bony reconstruction with a microvascular bone graft from the right iliac crest was performed in order to achieve a normal form and function of the mandible. Postoperative recovery of the patient was unremarkable, and no recurrence was reported. Dental rehabilitation and a good esthetic outcome were achieved by insertion of dental implants. Results: The performed interventions resulted in a complete anatomic and clinical cure. Conclusion: We suggest microvascular bone grafts from the anterior iliac crest as a valuable alternative in the long-term treatment of intraosseous AVMs, especially for extensive defects and in children. [Copyright &y& Elsevier]

The major blood supply to long bones occurs through the nutrient arteries, which enter through the nutrient foramina. This supply is essential during the growing period, during the early phases of ossification, and in procedures such as bone grafts, tumor resections, traumas, congenital pseudoarthrosis, and in transplant techniques in orthopedics. The present study analyzed the location and the number of nutrient foramina in the diaphysis of 885 long bones of the upper and lower limbs of adults: 174 humeri, 157 radii, 146 ulnae, 152 femora, 142 tibiae and 114 fibulae. The location of the nutrient foramina is predominant on the anterior aspect of the upper limb long bones, and on the posterior aspect of the lower limb long bones. The majority of the bones studied had a single nutrient foramen, which may represent a single source of blood supply. The mean foraminal index for the upper limb bones was 55.2% for the humerus, 35.7% for the radius, and 37.9% for the ulna, and for the lower limb bones, 43.7% for the femur. 32.7% for the tibia and 46.1% for the fibula. This study recorded data related to the population of Southern Brazil, providing ethnic data to be used for comparison and that may help in surgical procedures and in the interpretation of radiological images. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether there is any motion loss associated with the 1,2 intracompartmental supraretinacular artery (ICSRA) bone graft to the dorsal scaphoid. The null hypothesis is that placement of a vascularized bone graft in the dorsal scaphoid does not lead to a significant change in range of motion. Methods: Seven fresh-frozen cadaveric upper extremities were examined. Simulated 1,2 ICSRA bone grafts were harvested and placed into a dorsal trough made in the proximal scaphoid. Wrist motion measurements were performed before and after 1,2 ICSRA bone graft implantation. Results: There were no significant changes in wrist motion following 1,2 ICSRA bone graft implantation. Conclusions: Properly placed 1,2 ICSRA vascularized bone grafts for treatment of proximal scaphoid nonunions do not by themselves cause loss of wrist motion. Clinical Relevance: Loss of motion following the treatment of proximal scaphoid nonunions with properly placed 1,2 ICSRA vascularized bone grafts are due to factors other than the bone graft itself. [ABSTRACT FROM AUTHOR]

We present here two cases wherein we performed radiolunate fusion using vascularized radius graft with the vascular pedicle of the fourth extensor compartment artery (fourth ECA) for the treatment of Bain's grade 2A Kienböck disease with incongruity of the radiolunate joint. The dorsodistal radius graft was levered out and mobilized on the pedicle of the fourth ECA; then the vascularized dorsodistal radius was shifted 1 cm distally and bridges were created between the radius and the lunate. The radiolunate joint was completely fused in both cases at three months after surgery. The capitolunate joint maintained congruity after surgery. The Mayo wrist score was 75 points, and the DASH (JSSH version) score for the two cases was 2.5 and 4.2 points, respectively. Radiolunate fusion using the vascularized radius bridging procedure is one of the satisfactory methods for treating advanced Kienböck disease, especially in Bain's grade 2A cases. [ABSTRACT FROM AUTHOR]

Abstract: Disseminated lymphangiomatosis and Gorham–Stout disease are being considered as two forms of a single rare disease, characterized by a proliferation of lymphatic vessels, triggered by lymphangiogenic factors. There is no biological marker of the disease. Plasma VEGF might be a useful tool since the recent demonstration of its pivotal role in the mechanism of this disease. A 45-year-old woman with a history of disseminated lymphangiomatosis involving mediastinum, retroperitoneum, spleen and systemic bones for 29 years was treated with Interferon alpha 2b at a dosage of 7.5 to 15 million IU 3 times a week for 5 years. Plasma VEGF quantification was performed twice a year and showed a marked increase before therapy, which normalize after 18 months of treatment with Interferon. The normalization of plasma VEGF is correlated with the clinical improvement objectively appraised by a marked reduction of spleen lesions and significant improvement of the other damages in soft tissues and bones. Thus, we conclude that plasma VEGF determination should be considered for diagnosis and follow-up of the course and the treatment of disseminated lymphangiomatosis–Gorham–Stout disease. [Copyright &y& Elsevier]

Abstract: Old age-associated osteoporosis is related to diminished bone blood flow and impaired nitric oxide (NO)-mediated vasodilation of the bone vasculature. Endurance exercise training restores the age-associated reduction of vasodilation in numerous vascular beds, as well as improving bone properties. The purpose of this study was to determine whether functional improvements in the bone vasculature are associated with increased bone properties after an endurance training intervention. Young adult (4–6 months) and old (24–26 months) male Fischer-344 rats remained sedentary or were trained (15 m/min walking, 15° incline, 5 days/week, 10–12 weeks). Endothelium-dependent vasodilation of the femoral principal nutrient artery (PNA) was assessed in vitro using acetylcholine (ACh) and inhibitors of NO synthase (NOS) and cyclooxygenase (COX). PNA endothelium-dependent vasodilation was greater after training by 16% in young and by 24% in old animals. The NOS-mediated contribution to endothelium-dependent vasodilation was enhanced by 77% after training in old rats. Distal femur trabecular bone volume (BV/TV, %) was lower with old age in sedentary animals (young: 27±2%, old: 23±1%; P <0.05). Exercise-induced elevations in bone and marrow blood flow and the NOS signaling pathway were associated with greater BV/TV (young trained: 34±2%, old trained: 26±1%; P <0.05) relative to sedentary groups. These data demonstrate that training-induced increases in bone properties are associated with enhanced endothelium-dependent vasodilation through a NOS signaling pathway in the bone vasculature. [Copyright &y& Elsevier]

Abstract: Introduction: An anti-angiogenic effect of bisphosphonates has been reported in different experimental models. Zoledronic acid is currently administered in osteoporotic patients as a single 5 mg injection once a year and its vascular effect in bone has not been yet evaluated. Materials and methods: The vascular dose effect of a single injection of zoledronic acid was evaluated on healing vascularization developed under a bone chamber implanted on the calvaria of 30 rats. After 3 weeks of healing, the rats were randomized into 3 groups receiving an injection of either physiologic saline solution (PSS) or zoledronic acid tested at  120 μg/kg, the equivalent of a 5 mg dose of zoledronic acid in humans (Z120), and  400 μg/kg, a supra-pharmacologic dose (Z400). A longitudinal follow-up of the healing vascular network was carried out at days (D) 1, 3, 6, 9, 12, 15 and 28 after injection by intravital imaging. Variations in vascular density, total length of the vascular network and mean diameter of vascular network branches were determined by image analysis (Aphelion® software). Results: A decrease was observed in both vascular density and total length of the network in control and treated groups (time effect). No difference in variation in vascular density was observed between the PSS group and the Z120 group at any time point (p =NS). A trend to a higher decrease in vascular density was noted between D12 and D15 in the Z400 group. A significant decrease in total length was noted at D15 in the Z400 group (p =0.03) compared to the PSS group, whereas no change was noted in rats treated with  120 μg/kg compared to PSS rats on any of the follow-up days (p =0.2). No variation in mean diameter of vascular network branches was noted in any of the three groups at any of the follow-up days (p =0.53). Conclusion: A single injection of clinically relevant dosing regimens of zoledronic acid may not have a notable impact on vascularization in bone sites. The anti-angiogenic effect of bisphosphonates seems to express itself, in our model, at higher doses than those used in patients treated for osteoporosis. [Copyright &y& Elsevier]

Abstract: Glucocorticoid administration is required for many inflammatory and autoimmune diseases, but use of these drugs is associated with skeletal side effects including bone loss, fractures, and osteonecrosis. Fractures often occur without a reduction in bone mineral density, strongly suggesting that glucocorticoid excess adversely affects other aspects of bone strength. Although the primary effects of glucocorticoid excess on the skeleton are directly on bone cells, a vascular connection between these cells and the loss of bone strength appears likely. This review examines this connection and how it may explain the greater decline in bone strength than loss of bone mass that occurs with glucocorticoid excess. [Copyright &y& Elsevier]

The most important factor for the survival of thick three-dimensional tissues is the degree of vascularization. In this study, a modified arteriovenous loop (AVL) model was developed to prefabricate an axial vascularized tissue-engineered coral bone. In group A (n?=?28), an arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. The AVL was placed in a coral block (6???8???10 mm 3) as a vascular carrier. The complex was wrapped with polytetrafluoroethylene membrane and implanted subcutaneously. In group B (n?=?20), there was no vascular carrier, and the same dimensional coral was directly implanted beneath inguinal skin. After 2, 4, 6, and 8 weeks, the rabbits were perfused with heparinized saline (for scanning electron microscopy), India ink (for histological examination), and ethylene perchloride (for vascular casts) via the abdominal aorta. In group A, histology showed that newly formed vasculature extended over the surfaces and invaded the entire coral blocks. The vascular density was significantly superior to that in group B. Vascular casts showed that new blood vessels robustly sprouted from the AVL. Scanning electron microscopy demonstrated that there were minute sprouting cavities in the vascular endangium. In this model, an axial vascularized coral bone could be effectively constructed. [ABSTRACT FROM AUTHOR]

Objectives: To compare the dimensions of mandibular anatomical landmarks of human mandibles of three different chronological periods and seven different geographic regions. Methods: Cone beam computed tomography (CBCT) images were acquired from human mandibles of three different chronological periods (Neolithic, Medieval and 19-20th Century). The 19-20th Century consisted of seven human mandibular samples from different geographic locations. Image analysis consisted of comparing anatomic variability and dimensions of the mandibular, lingual and incisive canals, mental foramen and their relationship to specific reference teeth as such to determine geographic region and historic period variabilities. Results: There were statistically significant differences between the 19-20th Century group and the Medieval and Neolithic groups. The 19-20th Century group differed significantly in mandibular canal diameter, tooth root length, length of the lateral lingual canal. In addition, the group also differed from the Medieval sample for the lateral lingual foramen diameter and the midline lingual canal length. Furthermore, the prevalence of anatomic variations was significantly different for the geographic samples tested, with double mental foramina significantly more present in the Congolese sample, and significantly more lateral lingual canals noted in Indonesian and Greenland Eskimo samples. Conclusions: This study suggests that mandibular neurovascularisation may show some geographic as well as historic variation. Further studies on larger data samples are needed to verify this statement, as such that it can be potentially used in anthropology and forensic dentistry. More research is also needed to address whether the geographic and historic variations are linked, as well to investigate evolutionary trends in these structures. [ABSTRACT FROM AUTHOR]

Summary: Utilization of the metatarsal bones and interosseous muscles in foot reconstruction should be based on the vascular anatomy of the metatarsal bones and interosseous muscles. We studied the vascular anatomy of the metatarsal bones and the interosseous muscles to design a split metacarpal musculoosseous flap and dorsal interosseous muscle flap. Twenty-two feet from eleven cadavers that had been embalmed in formalin were studied. Dissection was done using a dissection microscope (×3.5), delineating meticulously the arcuate artery, dorsal metatarsal arteries and the small branches arising from the metatarsal arteries. The dorsal metatarsal arteries do not course at the midline of the interosseous muscles. The first dorsal metatarsal artery proceeds close to the first metatarsal bone in the first metatarsal space. While proceeding to the distal, it shoots out a branch that individually feeds the lateral head of the first dorsal metatarsal muscle and medial face of the second metatarsus, thereby feeding muscle and bone. Except for this branch, the first dorsal metatarsal gives off segmental and periosteal branches that individually feed the medial heads of the first dorsal metatarsal muscle and first metatarsal bone. The second, third and fourth metatarsal arteries proceed close to the third, fourth and fifth metatarsal bones in the metatarsal spaces. In these courses, the arteries give out segmental branches to both faces of the interosseous muscles and periosteal branches to the medial face of metatarsal bones. For defects or disease of the ankle bones, the metatarsal bones can be split at the medial border distally, and a split metatarsal musculoosseous flap, based proximally on the dorsal metatarsal artery, can be done. Distal intermetatarsal anastomoses between the dorsal and plantar vascular networks enables a split metatarsal musculoosseous flap based distally, including the dorsal metatarsal artery for bony defects of the proximal phalanx. [Copyright &y& Elsevier]

Much of the work aimed at elucidating the pathogenesis of osteonecrosis (ON) of the femoral head has focused on bone blood supply, with little attention to the surrounding synovial tissue (ST). We hypothesized that patients with ON exhibit synovial inflammation. Using immunohistological techniques, we found that a large population of patients with ON had synovial inflammation. Moreover, a population of ON patients had inflamed ST without having an inflammatory disease co-morbidity. The inflammatory infiltrate in these patients comprised primarily CD4+ T cells and CD68+ macrophages, the latter of which expressed increased levels of cellular adhesion molecules. Our results suggest the presence of a previously unrecognized population of ON patients without a diagnosed inflammatory co-morbidity and a highly inflammed synovium consisting primarily of a macrophage and CD4+ T-cell infi ltrate. [ABSTRACT FROM AUTHOR]

Abstract: Background: It has been shown that concomitant percutaneous transluminal angioplasty (PTA) of above-the-knee (ATK) and below-the-knee (BTK) arteries is highly beneficial for limb salvage in patients with critical limb ischaemia (CLI), but few published studies have specifically investigated outcomes in diabetic patients with CLI associated with isolated small BTK-vessel disease. This study aimed to evaluate the long-term results of successful PTA for limb salvage in such patients. Materials and methods: From among the 634 patients with CLI in our database, we retrospectively selected a consecutive series of 101 diabetics (16%) with 107 critically ischaemic limbs (33 Rutherford 5 and 74 Rutherford 6) and no critical ATK lesion, who underwent PTA on isolated BTK lesions. Results: The limb salvage rate was 93% after a mean follow-up of 1048±525 days (2.9±1.4 years). Transcutaneous oxygen tension significantly increased after 1 month (18.1±11.2 vs. 39.6±15.1; p <0.05). After 1 year, target-vessel re-stenosis had occurred in 42% of the non-amputated limbs, nine patients (9%) had died because of medical conditions unrelated to PTA and three patients had undergone repeat PTA for recurrent CLI. Conclusions: In our selected patient population with ischaemic diabetic foot and isolated BTK lesions, a successful endovascular procedure led to a high percentage of limb salvage at long-term follow-up. [Copyright &y& Elsevier]

Abstract: Adequate blood supply and sufficient mechanical stability are necessary for timely fracture healing. Damage to vessels impairs blood supply; hindering the transport of oxygen which is an essential metabolite for cells involved in repair. The degree of mechanical stability determines the mechanical conditions in the healing tissues. The mechanical conditions can influence tissue differentiation and may also inhibit revascularization. Knowledge of the actual conditions in a healing fracture in vivo is extremely limited. This study aimed to quantify the pressure, oxygen tension and temperature in the external callus during the early phase of bone healing. Six Merino-mix sheep underwent a tibial osteotomy. The tibia was stabilized with a standard mono-lateral external fixator. A multi-parameter catheter was placed adjacent to the osteotomy gap on the medial aspect of the tibia. Measurements of oxygen tension and temperature were performed for ten days post-op. Measurements of pressure were performed during gait on days three and seven. The ground reaction force and the interfragmentary movements were measured simultaneously. The maximum pressure during gait increased (p =0.028) from three (41.3 [29.2–44.1] mm Hg) to seven days (71.8 [61.8–84.8] mm Hg). During the same interval, there was no change (p =0.92) in the peak ground reaction force or in the interfragmentary movement (compression: p =0.59 and axial rotation: p =0.11). Oxygen tension in the haematoma (74.1 mm Hg [68.6–78.5]) was initially high post-op and decreased steadily over the first five days. The temperature increased over the first four days before reaching a plateau at approximately 38.5 °C on day four. This study is the first to report pressure, oxygen tension and temperature in the early callus tissues. The magnitude of pressure increased even though weight bearing and IFM remained unchanged. Oxygen tensions were initially high in the haematoma and fell gradually with a low oxygen environment first established after four to five days. This study illustrates that in bone healing the local environment for cells may not be considered constant with regard to oxygen tension, pressure and temperature. [Copyright &y& Elsevier]

Bone formation in a variety of contexts depends on angiogenesis; however, there are few reports of the vascular response to osteogenic skeletal loading. We used the rat forelimb compression model to characterize vascular changes after fatigue loading. The right forelimbs of 72 adult rats were loaded cyclically in vivo to one of four displacement levels, to produce four discrete levels of ulnar damage. Rats were killed 3-14 days after loading, and their vasculature was perfused with silicone rubber. Transverse histological sections were cut along the ulnar diaphysis. We quantified vessel number, average vessel area, total vessel area, and bone area. On day 3, we observed a dramatic periosteal expansion near the ulnar midshaft, with significant increases in periosteal vascularity; total vessel area was increased 250-450% (P < 0.001). Vascularity remained elevated on days 7 and 14. Vessel number and average vessel area were not correlated (P = 0.09) and contributed independently to total vascular increases. Bone area was not increased on day 3 but on days 7 and 14 was increased significantly in all displacement groups (P < 0.01) due to periosteal woven bone formation. Vascular and bone changes depended on longitudinal location (P < 0.001), with peak increases 2 mm distal to the midshaft. Vascular and bone changes also depended on displacement level (P < 0.005), with greater increases at higher levels of fatigue displacement. We conclude that skeletal fatigue loading induces a rapid increase in periosteal vascularity, followed by an increase in bone area. The angiogenic-osteogenic response is spatially coordinated and scaled to the level of the mechanical stimulus. [ABSTRACT FROM AUTHOR]

Purpose: Nonunion of the distal humerus after fracture or osteotomy is uncommon but can present an important clinical problem. Vascular insufficiency of bone may be an important contributing factor. The purpose of this study was to describe the intraosseous vascular anatomy of the distal humerus. Methods: Nine fresh-frozen upper extremity cadaver specimens were injected with India ink and Ward’s blue latex solution. A modified Spalteholz technique was used to show the intraosseous vascular anatomy. Results: The distal humeral diaphysis was supplied by a single nutrient artery. The lateral column was supplied predominately by posterior segmental vessels, whereas the medial column was supplied by anterior and posterior segmental vessels. The trochlea, olecranon fossa, and coronoid fossa were watershed areas. Conclusions: Our study shows the intraosseous vascular anatomy of the distal humerus is relatively consistent. There also appears to be a consistent trochlear vessel medially and small anterior perforating vessels in the lateral column that have not previously been described. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study was to assess the anatomy and vascularity of the lunate. The genesis of lunatomalacia requires some combination of vascular risk and mechanical predisposition. The findings will be correlated with the major existing theories of the cause of Kienböck''s disease. Methods: We studied 27 cadaver upper limbs using latex injection and the Spalteholz technique. We investigated the blood supply to the lunate. In 24 wrists we evaluated the incidence and distribution of anatomic features, arthrosis, and soft tissue lesions. We correlated the lunate morphology and ligaments disruptions with the arthritic changes. Results: The lunate morphology results as classified by Antuña-Zapico were five type I (20.8%), 18 type II (75%) and one type III (4.2%). The lunate was found to have a separate facet for the hamate in 11 cases (45.8%). The most common size of the facet was found to be 3 mm (range, 3–6 mm). Arthrosis was identified with most frequency in the radius (88.2%) and lunate (94.1%). The triangular fibrocartilage complex was found torn in 58.3%, the lunotriquetral interosseous ligament was torn in 20.8% and the scapholunate interosseous ligament (SLIL) was torn in 54.2% of the wrists. There was a correlation between the presence of arthrosis at the hamate and the presence of a lunate facet (P =0.027) and a correlation between the presence of a tear in the SLIL and arthrosis in the scaphoid (P =0.002). The nutrient vessels entered the lunate through the dorsal and volar poles in all the specimens. The dorsal intercarpal and radiocarpal arches supply blood to the lunate from a plexus of vessels located directly over the lunate''s dorsal pole. Vessels entered the dorsal aspect of the lunate through one to three foramina. One to five nutrient vessels were observed entering the volar pole through various ligament insertions, including the ligament of Testut-Kuentz (radio-scapho-lunate (RSL) ligament) and the radiolunate triquetrum ligament (or dorsoradial carpal ligament) and ulnar lunate triquetral ligament. Conclusions: The lunate had consistent dorsal and palmar arteries entering the bone in all the specimens. The blood supply and foramina number is greater in the volar pole of the lunate than the dorsal pole. The lunate blood supply comes from different ligaments. In the etiopathogeny of Kienböck''s disease it is possible that an acute or chronic, traumatic or non-traumatic injury of the vessel bearing ligaments, particularly because of their structure and the location of the RSL ligament, may have an important role in the appearance of lunate necrosis. [Copyright &y& Elsevier]

The determination of regional blood flow utilizing fluorescent microspheres (FMs) is an established method for numerous organs. Recent progress, in particular the automation of sample processing, has further improved this method. However, the FM method (reference sample technique), which allows repetitive measurement of regional organ blood flow, has so far not been used for the determination of blood flow in bone. The aim of the present study was to establish FM for the quantification of regional bone blood flow (RBBF). Female, anesthetized New Zealand rabbits (n = 6) received left ventricular injections of different amounts of FM at six subsequent time points. In order to examine the precision of RBBF determination, two different FM species were injected simultaneously at the sixth injection. At the end of the experiments the femoral and tibial condyles of each hind limb were removed and the fluorescence intensity in the tissue samples was measured by an automated procedure. In an in vitro study we have shown that acid digestion of the crystalline matrix has no effect on the fluorescence characteristics of FM. The determination of the number of spheres per tissue sample revealed that depending on the tissue sample size up to 3 x 10[sup6] spheres/injection were necessary to obtain about 400 microspheres in the individual bone samples. RBBF values of the tibial and femoral condyles did not differ at various injection intervals. The tibial blood flow values varied between 6.6 ± 1.1 and 8.5 ± 1.4 ml/min/100 g and were significantly higher than those of the femur (4.3 ± 1.1 to 6.0 ± 1.8 ml/min/100 g). The bone blood flow values obtained by simultaneous injection of two FM species correlated significantly (r = 0.96, slope = 1.06, intercept = 0.05), the mean difference was 0.39 ± 1.11 ml/min/100 g. Our data demonstrate that the measurement of RBBF by means of FM allows a valid determination of RBBF. [ABSTRACT FROM AUTHOR]

The article presents the results of a study which investigated the possibility that histocompatibility could be induced by soaking bone in plasma from a histocompatible source. An overview of related previous research is provided, along with details of the experimental protocol, which involved implanting bone samples in the eyes of mice. It was found that bone soaked in plasma did not develop a blood supply.

Abstract: Osteonecrosis of femoral head (ONFH) is a challenging disease. Regardless of underlying causes, the ultimate result in all cases is disruption of femoral head blood supply. Once the disease starts, it is progressive in 80% of cases. Since the majority of the affected individuals are young, every effort should be focused on preserving the patients own femoral head. These years, the role of angiogenic growth factors has been investigated with promising results in animal models of ONFH. Erythropoietin (EPO) is a well known hormone that has been used in treatment of chronic anemia for many years with few side effects. Considering the angiogenic properties of EPO, we hypothesize that local delivery of recombinant human EPO during core decompression will enhance bone regeneration in ONFH. In this way we also can avoid systemic side effects of EPO. [Copyright &y& Elsevier]

Replacement of nonvascular cartilage by bone and bone marrow is a critical step in bone development. In a recent issue of Developmental Cell, report that a distinct population of immature precursors of bone-forming cells migrate into the cartilage in intimate association with invading blood vessels. [ABSTRACT FROM AUTHOR]

Summary: The most accepted part of the aetiology of Perthes’ disease is an intermittent arterial occlusion. Many different reports now also suggest that some mechanical factor plays a role. In search of mechanical differences between normal hips and Perthes hips, many secondary morphologic differences of the proximal femur and the acetabulum are known. Recent research by the author has shown morphological changes of the acetabulum, independent of Perthes’ disease in a large part of patients. In particular, retroversion of the acetabulum was found in a large part of adults who suffered from Perthes’ disease as a child, and even in children who just developed Perthes’ disease. The author suggest a relation of the two entities and hypotheses that due to the acetabular retroversion, there may be an intermittent, movement depending abnormal loading pressure on the dorsal femoral head–neck junction and the local blood vessels, which can lead to insufficient blood supply of the femoral epiphysis and to local necrosis, as these vessels are the only blood supply to the femoral epihysis in children. [Copyright &y& Elsevier]

Describes the diagnostic tests for bone hemangiomas in Canada. Sensitivity of magnetic resonance imaging to marrow disorders; Computed tomography as the modality of choice to distinguish between malignant disease and hemangioma; Appearance of the bone which is pathognomonic of the disease; Implication of the image on disease management.

A correction to the article " Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone" in the March 20, 2014 issue is presented, which discusses the administration of deferoxamine mesylate (DFM) for microtomographical analysis.

This article presents images representing diffusely increased glucose consumption in the articular cavity of the left knee and focal glucose hypermetabolism in the left tibia adjacent to the prosthesis confirmed suspicion of infection following total left knee replacement in a patient with chronic fever and presence of Staphylococcus aureus in blood samples.