Quality Of Bone Structure Research Articles

Selected musculoskeletal disorders in patients with thyroid dysfunction, diabetes, and obesity.

Many medical conditions affect the skeletal system and constitute independent risk factors for fractures. The action of thyroid hormones is necessary to maintain adequate development, mineralization, and bone strength. Untreated hyperthyroidism can lead to a decrease in bone mineral density (BMD), osteoporosis, and pathological fractures. In hypothyroidism, the changes in the quality of bone structure lead to an increase in the frequency of fractures. Excessive body weight negatively impacts fracture risk, increases the risk of osteoarthritis and accelerates the development of rheumatoid arthritis and osteoporosis. Type 1 and type 2 diabetes are associated with an increased risk of bone fractures despite different etiopathogenesis due to the duration of the disease and the pro-inflammatory state, the incorporation of advanced glycation end products (AGEs) into the bone matrix, and microvascular disorders. This study summarizes the current literature on the influence of thyroid dysfunction, obesity, and diabetes on the skeletal system.

Intrauterine alcohol exposure delays growth and disturbs trabecular morphology in 3-week-old Sprague − Dawley rat femur

Introduction: The consequence of gestational alcohol exposure ranges from stillbirth to miscarriage and fetal alcohol syndrome (FAS). FAS is one of the deleterious causes of congenital disabilities, mental and growth retardation. Several studies suggest that low birth weight and impaired bone growth, as well as a decrease in mineralization in utero, may reduce peak bone mass and increase the risk of fractures and osteoporosis later in life. Therefore, the aim of this study was to determine the effects of intrauterine alcohol exposure on the internal architecture of the femur. Material and Methods: Time-mated (n = 13) pregnant Sprague − Dawley dams were assigned to either the ethanol (n = 5), saline control (n = 5) or untreated control (n = 3) group. The former two groups were treated with 0.015 ml/g of 25.2% ethanol and 0.9% saline for the first 19 days of gestation, respectively. The untreated group received no treatment. Once born, the pups were weaned at 21 days. These rats were then terminated. From each dam, two pups were collected resulting in ethanol (n = 10), saline controls (n = 10), and untreated controls (n = 6). The femora of the pups were dissected and scanned using a 3D-μCT scanner (Nikon XTH 225 L) at 15 μm resolution. Trabecular and cortical parameters were analyzed using Volume Graphics Studio® software following reconstruction. Results: We found altered trabecular parameters in the alcohol exposed group. The diaphyseal cortical and medullary cavity proportions were also affected, particularly in the midshaft. Discussion and Conclusion: These results indicate that gestational alcohol exposure may lower bone structural quality by disturbing the internal morphology of the osseous tissue.

Aromatic Bis[aminomethylidenebis(phosphonic)] Acids Prevent Ovariectomy-Induced Bone Loss and Suppress Osteoclastogenesis in Mice.

Osteoporosis is a skeletal disease associated with excessive bone turnover. Among the compounds with antiresorptive activity, nitrogen-containing bisphosphonates play the most important role in antiosteoporotic treatment. In previous studies, we obtained two aminomethylidenebisphosphonates—benzene-1,4-bis[aminomethylidene(bisphosphonic)] (WG12399C) acid and naphthalene-1,5-bis[aminomethylidene(bisphosphonic)] (WG12592A) acid—which showed a significant antiproliferative activity toward J774E macrophages, a model of osteoclast precursors. The aim of these studies was to evaluate the antiresorptive activity of these aminobisphosphonates in ovariectomized (OVX) Balb/c mice. The influence of WG12399C and WG12592A administration on bone microstructure and bone strength was studied. Intravenous injections of WG12399C and WG12592A bisphosphonates remarkably prevented OVX-induced bone loss; for example, they sustained bone mineral density at control levels and restored other bone parameters such as trabecular separation. This was accompanied by a remarkable reduction in the number of TRAP-positive cells in bone tissue. However, a significant improvement in the quality of bone structure did not correlate with a parallel increase in bone strength. In ex vivo studies, WG12399C and WG12592A remarkably bisphosphonates reduced osteoclastogenesis and partially inhibited the resorptive activity of mature osteoclasts. Our results show interesting biological activity of two aminobisphosphonates, which may be of interest in the context of antiresorptive therapy.

Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector.

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1–34 and 107–139); mcPTHrP 1–34+107–139 using a minicircle vector. We also transfected mcPTHrP 1–34+107–139 into human mesenchymal stem cells (MSCs) and generated Thru 1–34+107–139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1–34+107–139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1–34+107–139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1–34+107–139 using the minicircle technology for the treatment of osteoporosis.

Spaceflight-Induced Bone Tissue Changes that Affect Bone Quality and Increase Fracture Risk.

Bone mineral density and systemic factors are used to assess skeletal health in astronauts. Yet, even in a general population, these measures fail to accurately predict when any individual will fracture. This review considers how long-duration human spaceflight requires evaluation of additional bone structural and material quality measures that contribute to microgravity-induced skeletal fragility. In both humans and small animal models following spaceflight, bone mass is compromised via reduced bone formation and elevated resorption levels. Concurrently, bone structural quality (e.g., trabecular microarchitecture) is diminished and the quality of bone material is reduced via impaired tissue mineralization, maturation, and maintenance (e.g., mediated by osteocytes). Bone structural and material quality are both affected by microgravity and may, together, jeopardize astronaut operational readiness and lead to increased fracture risk upon return to gravitational loading. Future studies need to directly evaluate how bone quality combines with diminished bone mass to influence bone strength and toughness (e.g., resistance to fracture). Bone quality assessment promises to identify novel biomarkers and therapeutic targets.

Type 1 diabetes onset at young age is associated with compromised bone quality.

Women with type 1 diabetes (T1D) are at increased risk for fracture. We studied the association of T1D and young age at T1D onset (T1D onset before 20 years) on bone structural quality. 24 postmenopausal women with T1D (mean age 60.9 years, mean T1D duration 41.7 years) and 22 age, sex- and body mass index (BMI)-matched controls underwent dual X-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the lumbar spine, hip and distal radius. Bone mass, geometry and estimated bone strength were assessed at distal and shaft of non-dominant radius and tibia using peripheral quantitative computed tomography (pQCT). Postmenopausal women with T1D had lower trabecular volumetric bone mineral density (vBMD) (LSM ± SEM; 166.1 ± 8.2 vs 195.9 ± 8.3 mg/cm3, p = 0.02) and compressive bone strength (24.6 ± 1.8 vs 30.1 ± 1.9 mg2/mm4, p = 0.04) at the distal radius compared to controls adjusting for age, BMI and radius length. At the distal radius, patients with young onset T1D had lower total vBMD (258.7 ± 19.7 vs 350.8 ± 26.1 mg/cm3, p = 0.02) and trabecular vBMD (141.4 ± 11.6 vs 213.6 ± 15.4 mg/cm3, p = 0.003) compared to adult onset T1D patients adjusting for age, BMI and the radius length. At the tibial shaft, young onset T1D patients had larger endosteal circumference (39.1 ± 1.2 vs 32.1 ± 1.6 mm, p = 0.005) with similar periosteal circumference (67.1 ± 0.9 vs 65.1 ± 1.2 mm, p = 0.2) resulting in reduced cortical thickness (4.4 ± 0.1 vs 5.2 ± 0.1 mm, p = 0.004) compared to adult onset T1D patients adjusting for age, BMI and the tibia length. There was no difference in the lumbar spine, femoral neck, total hip and distal radius DXA-measured aBMD between subjects with T1D and controls. T1D is associated with lower trabecular vBMD at the distal radius. T1D onset before age 20 is associated with cortical bone size deficits at the tibial shaft.

Estimating the mechanical competence parameter of the trabecular bone: a neural network approach

Abstract Introduction The mechanical competence parameter (MCP) of the trabecular bone is a parameter that merges the volume fraction, connectivity, tortuosity and Young modulus of elasticity, to provide a single measure of the trabecular bone structural quality. Methods As the MCP is estimated for 3D images and the Young modulus simulations are quite consuming, in this paper, an alternative approach to estimate the MCP based on artificial neural network (ANN) is discussed considering as the training set a group of 23 in vitro vertebrae and 12 distal radius samples obtained by microcomputed tomography (μCT), and 83 in vivo distal radius magnetic resonance image samples (MRI). Results It is shown that the ANN was able to predict with very high accuracy the MCP for 29 new samples, being 6 vertebrae and 3 distal radius bones by μCT and 20 distal radius bone by MRI. Conclusion There is a strong correlation (R2 = 0.97) between both techniques and, despite the small number of testing samples, the Bland-Altman analysis shows that ANN is within the limits of agreement to estimate the MCP.

Bone Banking in a Traumatologic Department: A Ten-Year Analysis

Background: Orthopedic and traumatologic departments have the choice of conducting an own bone bank in which grafts are prepared and stored, or purchasing costly bone grafts from professional providers. The aim of the study was to retrospectively analyse the bone bank affiliated with the traumatology department in the ten-year time period from 2001-2010. Patients and Methods: Altogether 1035 patients who underwent a primary hip replacement were included as potential donors. 632 patients were treated with a coxarthritis (CA) and 403 with a femoral neck fracture (FNF). Results: The bone donation was deferred in 731 (70,6%) and conducted in 304 (29,4%) patients. The majority of the deferrals were due to the maturity (age above 75 years) of the patients and an osteoporotic bone structure of the graft. Other reasons for deferral were a positive donor history, incomplete donation documents, and previous osteosynthesis of the proximal femur or acetabulum. The rate for exclusion was significantly higher in the FNF group, which was based on the difference of age, bone structure quality, and the non-elective setting of the operative treatment. Conclusion: In summary, bone donations from urgently hospitalised patients with a FNF have a significantly higher deferral rate than electively planned patients with CA.

Role of Vanadium (V) in the Differentiation of C3H10t1/2 Cells Towards Osteoblast Lineage: A Comparative Analysis with Other Trace Elements

In recent time, vanadium compounds are being used as antidiabetic drug and in orthopedic implants. However, the exact role of this incorporated vanadium in improving the quality of bone structure and morphology is not known. The impact of vanadium ion was studied and compared to other trace metal ions with respect to the proliferation and osteoblast differentiation of C3H10t1/2 cells. Toxicity profile of these trace metal ions revealed a descending toxicity trend of Fe(2+) > Zn(2+) > Cu(2+) > Co(2+) > Mn(2+) > V(5+) > Cr(2+). The effect of vanadium and other trace metal ions on osteoblast differentiation was evaluated by culturing the cells for 10days in osteoblastic medium supplemented with different trace ions at concentrations lower than their cytotoxic doses. The results indicated that vanadium has maximum impact on the induction of osteoblast differentiation by upregulating alkaline phosphatase activity and mineralization by up to 145 and 150%, respectively (p < 0.05), over control. Cu(2+) and Zn(2+) had a mild inhibitory effect, while Mn(2+), Fe(2+), and Co(2+) demonstrated a clear decrease in osteoblast differentiation when compared to the control. The data as presented here demonstrate that orthopedic implants, if supplemented with trace metals like vanadium, may provide a source of better model for bone formation and its turnover.

Implant stability is affected by local bone microstructural quality

It is known that low bone quality, caused for instance by osteoporosis, not only increases the risk of fractures, but also decreases the performance of fracture implants; yet the specific mechanisms behind this phenomenon are still largely unknown. We hypothesized that especially peri-implant bone microstructure affects implant stability in trabecular bone, to a greater degree than more distant bone. To test this hypothesis we performed a computational study on implant stability in trabecular bone. Twelve humeral heads were measured using micro-computed tomography. Screws were inserted digitally into these heads at 25 positions. In addition, at each screw location, a virtual biopsy was taken. Bone structural quality was quantified by morphometric parameters. The stiffness of the 300 screw-bone constructs was quantified as a measure of implant stability. Global bone density correlated moderately with screw-bone stiffness (r2=0.52), whereas local bone density was a very good predictor (r2=0.91). The best correlation with screw-bone stiffness was found for local bone apparent Young's modulus (r2=0.97), revealing that not only bone mass but also its arrangement in the trabecular microarchitecture are important for implant stability. In conclusion, we confirmed our hypothesis that implant stability is affected by the microstructural bone quality of the trabecular bone in the direct vicinity of the implant. Local bone density was the best single morphometric predictor of implant stability. The best predictability was provided by the mechanical competence of the peri-implant bone. A clinical implication of this work is that apparently good bone stock, such as assessed by DXA, does not guarantee good local bone quality, and hence does not guarantee good implant stability. New tools that could quantify the structural or mechanical quality of the peri-implant bone may help improve the surgical intervention in reaching better clinical outcomes for screw fixation.

Dietary vitamin K intake is associated with bone quantitative ultrasound measurements but not with bone peripheral biochemical markers in elderly men and women

Vitamin K may have a protective role against bone loss and osteoporotic fractures associated to aging, although data in humans are inconsistent and the mechanisms involved are still unknown. The main objective of the study was to assess the associations between vitamin K intake, bone density, bone structure quality and biochemical bone metabolism markers in elderly subjects. We also analyzed the relationship between changes in vitamin K intake and the evolution of bone quality markers after two years of follow-up. Cross-sectional analysis was carried out on 365 elderly subjects, 200 of whom were also included in a 2-year longitudinal follow-up study. Usual dietary intakes were assessed using a semi-quantitative 137-item food frequency questionnaire (FFQ). Vitamin K intake was estimated using the USDA database. Bone biochemical markers were measured in a subset of 125 subjects. Quantitative ultrasound assessment (QUS) was performed at the calcaneus to estimate bone mineral density (BMD), speed of sound (SOS), broadband ultrasound attenuation (BUA) and the quantitative ultrasound index (QUI). Dietary intake of vitamin K was significantly associated with higher BMD and better QUS. No significant associations were found between vitamin K intake and bone biochemical markers. Those subjects who increased their vitamin K intake showed a lower loss of BMD, a lower decrease in SOS and a nonsignificant increase in BUA. High dietary vitamin K intake was associated with superior bone properties. Moreover, an increase in dietary vitamin K was significantly related to lower losses of bone mineral density and smaller increases in the porosity and elasticity attributed to aging, which helps to explain the previously described protective effect of vitamin K intake against osteoporotic fractures.

The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture

The aim of this study was to assess the effect of type 1 diabetes mellitus (DM) on the structure of mandibular bone and on the changes of alveolar/jaw bone formation. Experimental DM was induced in 3-wk-old male Wistar rats by a single dose of 60 mg/kg body weight of streptozotocin. All rats were injected with calcein on days 21 and 28. The rats were killed when 8 wk of age. Bone structure was analyzed by bone histomorphometry, microcomputed tomography (micro-CT), and histological section. Histomorphometric analysis showed that the mineral apposition and the bone formation rates in most of the mandibular regions were significantly decreased in the DM group compared with the control group. Micro-CT analysis showed significant deterioration of the bone quality in rats with DM. For a histometric measure of bone resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The number of osteoclasts was significantly lower in the rats with DM than in the controls. These findings suggest that uncontrolled DM decreases mandibular bone formation, reduces the rate of bone turnover in the alveolar wall surrounding the root, and affects the quality of bone structure resulting in retardation of its skeletal development.

Volumetric Topological Analysis: A Novel Approach for Trabecular Bone Classification on the Continuum Between Plates and Rods

Trabecular bone (TB) is a complex quasi-random network of interconnected plates and rods. TB constantly remodels to adapt to the stresses to which it is subjected (Wolff's Law). In osteoporosis, this dynamic equilibrium between bone formation and resorption is perturbed, leading to bone loss and structural deterioration. Both bone loss and structural deterioration increase fracture risk. Bone's mechanical behavior can only be partially explained by variations in bone mineral density, which led to the notion of bone structural quality. Previously, we developed digital topological analysis (DTA) which classifies plates, rods, profiles, edges, and junctions in a TB skeletal representation. Although the method has become quite popular, a major limitation of DTA is that it provides only hard classifications of different topological entities, failing to distinguish between narrow and wide plates. Here, we present a new method called volumetric topological analysis (VTA) for regional quantification of TB topology. At each TB location, the method uniquely classifies its topology on the continuum between perfect plates and perfect rods, facilitating early detections of TB alterations from plates to rods according to the known etiology of osteoporotic bone loss. Several new ideas, including manifold distance transform, manifold scale, and feature propagation have been introduced here and combined with existing DTA and distance transform methods, leading to the new VTA technology. This method has been applied to multidetector computed tomography (CT) and micro-computed tomography ( μCT) images of four cadaveric distal tibia and five distal radius specimens. Both intra- and inter-modality reproducibility of the method has been examined using repeat CT and μCT scans of distal tibia specimens. Also, the method's ability to predict experimental biomechanical properties of TB via CT imaging under in vivo conditions has been quantitatively examined and the results found are very encouraging.

Precision Study of Various QUS Devices Compared with DXA Data in Korean Women

Vitamin K may have a protective role against bone loss and osteoporotic fractures associated to aging, although data in humans are inconsistent and the mechanisms involved are still unknown. The main objective of the study was to assess the associations between vitamin K intake, bone density, bone structure quality and biochemical bone metabolism markers in elderly subjects. We also analyzed the relationship between changes in vitamin K intake and the evolution of bone quality markers after two years of follow-up.Cross-sectional analysis was carried out on 365 elderly subjects, 200 of whom were also included in a 2-year longitudinal follow-up study. Usual dietary intakes were assessed using a semi-quantitative 137-item food frequency questionnaire (FFQ). Vitamin K intake was estimated using the USDA database. Bone biochemical markers were measured in a subset of 125 subjects. Quantitative ultrasound assessment (QUS) was performed at the calcaneus to estimate bone mineral density (BMD), speed of sound (SOS), broadband ultrasound attenuation (BUA) and the quantitative ultrasound index (QUI).Dietary intake of vitamin K was significantly associated with higher BMD and better QUS. No significant associations were found between vitamin K intake and bone biochemical markers. Those subjects who increased their vitamin K intake showed a lower loss of BMD, a lower decrease in SOS and a nonsignificant increase in BUA.High dietary vitamin K intake was associated with superior bone properties. Moreover, an increase in dietary vitamin K was significantly related to lower losses of bone mineral density and smaller increases in the porosity and elasticity attributed to aging, which helps to explain the previously described protective effect of vitamin K intake against osteoporotic fractures.

Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: The OFELY Study

Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density (BMD), such as low body weight, history of fractures, and clinical risk factors for falls. Their relevance in predicting all fragility fractures in all postmenopausal women, including younger ones, is unknown. The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women. We prospectively followed for 5.3 ± 1.1 years a cohort of 672 healthy postmenopausal women (mean age 59.1 ± 9.8 years). Information on social and professional conditions, demographic data, current and past medical history, fracture history, medication use, alcohol consumption, caffeine consumption, daily calcium intake, cigarette smoking, family history of fracture, and past and recent physical activity was obtained. Anthropometric and total hip bone mineral density measurements were made. Incident falls and fractures were ascertained every year. We observed 81 osteoporotic fractures (annual incidence, 21 per 1000 women/year). The final model consisted of seven independent predictors of incident osteoporotic fractures: age ≥ 65 years, odds ratio estimate (OR), 1.90 [95% confidence interval (CI) 1.04–3.46], past falls, OR, 1.76 (CI 1.00–3.09), total hip bone mineral density (BMD) ≤ 0.736 g/cm 2, OR, 3.15 (CI 1.75–5.66), left grip strength ≤ 0.60 bar, OR, 2.05 (CI 1.15–3.64), maternal history of fracture, OR, 1.77 (CI 1.01–3.09), low physical activity, OR, 2.08 (CI 1.17–3.69), and personal history of fragility fracture, OR, 3.33 (CI 1.75–5.66). In contrast, body weight, weight loss, height loss, smoking, neuromuscular coordination assessed by three tests, and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables. We found that some—but not all—previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women, although they differed somewhat from those predicting specifically hip fractures in elderly women. These risk factors appear to reflect quality of bone structure (previous fragility fracture), lifestyle habits (physical activity), muscle function and health status (grip strength), heredity (maternal history of fracture), falls, and aging. Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women.