Changes In Bone Architecture Research Articles

Ethanol consumption in non-human primates alters plasma markers of bone turnover but not tibia architecture

Ethanol consumption is associated with positive, negative, and neutral effects on the skeletal system. Our previous work using a nonhuman primate model of voluntary ethanol consumption showed that chronic ethanol use has an impact on skeletal attributes, most notably on biochemical markers of bone turnover. However, these studies were limited by small sample sizes and resulting lack of statistical power. Here, we applied a machine learning framework to integrate data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. Specifically, we analyzed the influence of ethanol consumption on biomarkers of bone turnover and cancellous and cortical bone architecture in tibia. We hypothesized that chronic ethanol use for 6 months to 2.5 years would result in measurable changes to cancellous features and the biochemical markers compared to control animals. We observed a decrease in bone turnover in monkeys exposed to ethanol; however, we did not find that ethanol consumption resulted in measurable changes in bone architecture.

Bone Health in Patients With Type 2 Diabetes.

The association between type 2 diabetes mellitus (T2DM) and skeletal fragility is complex, with effects on bone at the cellular, molecular, and biomechanical levels. As a result, people with T2DM, compared to those without, are at increased risk of fracture, despite often having preserved bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). Maladaptive skeletal loading and changes in bone architecture (particularly cortical porosity and low cortical volumes, the hallmark of diabetic osteopathy) are not apparent on routine DXA. Alternative imaging modalities, including quantitative computed tomography and trabecular bone score, allow for noninvasive visualization of cortical and trabecular compartments and may be useful in identifying those at risk for fractures. Current fracture risk calculators underestimate fracture risk in T2DM, partly due to their reliance on BMD. As a result, individuals with T2DM, who are at high risk of fracture, may be overlooked for commencement of osteoporosis therapy. Rather, management of skeletal health in T2DM should include consideration of treatment initiation at lower BMD thresholds, the use of adjusted fracture risk calculators, and consideration of metabolic and nonskeletal risk factors. Antidiabetic medications have differing effects on the skeleton and treatment choice should consider the bone impacts in those at risk for fracture. T2DM poses a unique challenge when it comes to assessing bone health and fracture risk. This article discusses the clinical burden and presentation of skeletal disease in T2DM. Two clinical cases are presented to illustrate a clinical approach in assessing and managing fracture risk in these patients.

Influence of a change in activity regime on femoral bone architecture and failure behaviour.

The incidence and morbidity of femoral fractures increases drastically with age. Femoral architecture and associated fracture risk are strongly influenced by loading during physical activities and it has been shown that the rate of loss of bone mineral density is significantly lower for active individuals than inactive. The objective of this work is to evaluate the impact of a cessation of some physical activities on elderly femoral structure and fracture behaviour. The authors previously established a biofidelic finite element model of the femur considered as a structure optimised to loading associated with daily activities. The same structural optimisation algorithm was used here to quantify the changes in bone architecture following cessation of stair climbing and sit-to-stand. Side fall fracture simulations were run on the adapted bone structures using a damage elasticity formulation. Total cortical and trabecular bone volume and failure load reduced in all cases of activity cessation. Bone loss distribution was strongly heterogeneous, with some locations even showing increased bone volume. This work suggests that maintaining the physical activities involved in the daily routine of a young healthy adult would help reduce the risk of femoral fracture in the elderly population by preventing bone loss.

Relationship of the bone phenotype of the Klotho mutant mouse model of accelerated aging to changes in skeletal architecture that occur with chronological aging.

Due to the relatively long life span of rodent models, in order to expediate the identification of novel therapeutics of age related diseases, mouse models of accelerated aging have been developed. In this study we examined skeletal changes in the male and female Klotho mutant (kl/kl) mice and in male and female chronically aged mice to determine whether the accelerated aging bone phenotype of the kl/kl mouse reflects changes in skeletal architecture that occur with chronological aging. 2, 6 and 20-23 month old C57BL/6 mice were obtained from the National Institute of Aging aged rodent colony and wildtype and kl/kl mice were generated as previously described by M. Kuro-o. Microcomputed tomography analysis was performed ex vivo to examine trabecular and cortical parameters from the proximal metaphyseal and mid-diaphyseal areas, respectively. Serum calcium and phosphate were analyzed using a colorimetric assay. The expression of duodenal Trpv6, which codes for TRPV6, a vitamin D regulated epithelial calcium channel whose expression reflects intestinal calcium absorptive efficiency, was analyzed by quantitative real-time PCR. Trabecular bone volume (BV/TV) and trabecular number decreased continuously with age in males and females. In contrast to aging mice, an increase in trabecular bone volume and trabecular number was observed in both male and female kl/kl mice. Cortical thickness decreased with advancing age and also decreased in male and female kl/kl mice. Serum calcium and phosphate levels were significantly increased in kl/kl mice but did not change with age. Aging resulted in a decline in Trpv6 expression. In the kl/kl mice duodenal Trpv6 was significantly increased. Our findings reflect differences in bone architecture as well as differences in calcium and phosphate homeostasis and expression of Trpv6 between the kl/kl mutant mouse model of accelerated aging and chronological aging. Although the Klotho deficient mouse has provided a new understanding of the regulation of mineral homeostasis and bone metabolism, our findings suggest that changes in bone architecture in the kl/kl mouse reflect in part systemic disturbances that differ from pathophysiological changes that occur with age including dysregulation of calcium homeostasis that contributes to age related bone loss.

P-12 Postpartum vertebral compressive fractures in a young female with osteoporosis - A case report

Abstract Introduction Osteoporosis is а metabolic disorder characterized by low bone mass and deep changes in bone architecture that lead to an increased vertebral or hip fracture in elderly. Osteoporosis in young population is a very rare condition especially when is associated with compressive fractures. Pregnancy and postpartum-related osteoporosis is condition that occurs in the last trimester of pregnancy оr in the first months of lactation. It is self-limited condition that return to normal after 12-18 months. In rare cases leаds to spinal compressive fractures. Clinical Case We present a 33-year-old female with back pain that occurs after birth during the early lactation period. In consultation with an orthopedic surgeon, an X-ray was made on the thoracolumbar spinal column with a finding of vertebral compressive fractures. A DEXA scan (double energy-X rays of absorptiometry) is also made with the finding of vertebral osteoporosis and hip osteopenia. We calculate BMI and perform blood tests for vitamin D3, calcium, hormones and markers for bone metabolism. This was our patient's first birth, she was thin with height 157 cm, weight 42 kg and calculated BMI-17. Blood test showed very low concentration of vitamin D3- 16 ng/ml (20-44) with normal level of calcium- 1,20 mmol/l (1,10-1,40) and PTH-31,01 pg./ml (15-65). Thyroid, gonadal and adrenal axis was with normal function. We told the patient to stop the lactation and to take a supplementation of vitamin D3 2000 IE, Calcium 1000 mg and bisphosphonates (alendronate). After two years of treatment, we made a control DEXA scan. Our patient now has vertebral osteopenia, normal serum concentration of vitamin D (44 ng/ml) and her weight is 48 kg. She feels good, has no pain and no new fractures. Conclusion Pregnancy and lactation increase need for calcium and this condition is complemented by increased intestinal absorption of calcium and increased bone resorption of the mother's skeleton. Risk factors for low bone density are deficit of 1-25 OH vitamin D3, malnutrition, low body mass index, treatment with low dose of enoxaparin (LMWH), physical inactivity. Our patient has an increased risk of low bone density (she has a low body mass index, low serum concentration of 1–25 OH vitamin D3 and this was her first pregnancy). Normal serum level 1–25 OH vitamin D concentration is required to establish calcium metabolism and prevent low bone density, osteopenia or osteoporosis. Antiresorptive therapy with bisphosphonates lead to rapid improvement in bone density, prevent new fractures and relieves pain. Treatment of postpartum osteoporosis is debatable because this condition is reversible, so when we decide to treat or not to treat, we must consider present of fractures, pain and plan for future pregnancy.

Skeletal complications in acromegaly.

Hypersecretion of growth hormone (GH) is rare and typically results from a pituitary functional tumor - somatotropinoma. It leads to excessive linear bone growth and manifests as gigantism if occurring in childhood and adolescence, before the closure of epiphyses or as a acromegaly in adulthood. The excess of GH impacts bone metabolism directly as well as indirectly through increased insulin-like growth factor 1 (IGF-1). In acromegaly as a consequence of overproduction of GH and IFG-1 and the influence of these hormones on bone osteoblasts, bone metabolism, growth and density increase. However, bone turnover is accelerated causing impaired bone microstructure and strength, which may lead to increased risk of vertebral fractures irrespective of normal bone mineral density. Apart from the changes in bone architecture, acromegaly also results in a degenerative joint disease of a different nature than primary osteoarthritis. Moreover, acromegaly leads to cardiovascular, metabolic and respiratory complications, and thus significantly impairs the quality of life. In this review, authors summarize the pathophysiology, diagnosis, and treatment of bone and joint disease in acromegaly.

MRI texture analysis of acetabular cancellous bone can discriminate between normal, cam positive, and cam-FAI hips.

To compare the MRI texture profile of acetabular subchondral bone in normal, asymptomatic cam positive, and symptomatic cam-FAI hips and determine the accuracy of a machine learning model for discriminating between the three hip classes. A case-control, retrospective study was performed including 68 subjects (19 normal, 26 asymptomatic cam, 23 symptomatic cam-FAI). Acetabular subchondral bone of unilateral hip was contoured on 1.5T MR images. Nine first-order 3D histogram and 16s-order texture features were evaluated using specialized texture analysis software. Between-group differences were assessed using Kruskal-Wallis and Mann-Whitney U tests, and differences in proportions compared using chi-square and Fisher's exact tests. Gradient-boosted ensemble methods of decision trees were created and trained to discriminate between the three groups of hips, with percent accuracy calculated. Sixty-eight subjects (median age 32 (28-40), 60 male) were evaluated. Significant differences among all three groups were identified with first-order (4 features, all p ≤ 0.002) and second-order (11 features, all p ≤ 0.002) texture analyses. First-order texture analysis could differentiate between control and cam positive hip groups (4 features, all p ≤ 0.002). Second-order texture analysis could additionally differentiate between asymptomatic cam and symptomatic cam-FAI groups (10 features, all p ≤ 0.02). Machine learning models demonstrated high classification accuracy of 79% (SD 16) for discriminating among all three groups. Normal, asymptomatic cam positive, and cam-FAI hips can be discriminated based on their MRI texture profile of subchondral bone using descriptive statistics and machine learning algorithms. Texture analysis can be performed on routine MR images of the hip and used to identify early changes in bone architecture, differentiating morphologically abnormal from normal hips, prior to onset of symptoms. • MRI texture analysis is a technique for extracting quantitative data from routine MRI images. • MRI texture analysis demonstrates that there are different bone profiles between normal hips and those with femoroacetabular impingement. • Machine learning models can be used in conjunction with MRI texture analysis to accurately differentiate between normal hips and those with femoroacetabular impingement.

Aging and Bone Metabolism.

Changes in bone architecture and metabolism with aging increase the likelihood of osteoporosis and fracture. Age-onset osteoporosis is multifactorial, with contributory extrinsic and intrinsic factors including certain medical problems, specific prescription drugs, estrogen loss, secondary hyperparathyroidism, microenvironmental and cellular alterations in bone tissue, and mechanical unloading or immobilization. At the histological level, there are changes in trabecular and cortical bone as well as marrow cellularity, lineage switching of mesenchymal stem cells to an adipogenic fate, inadequate transduction of signals during skeletal loading, and predisposition toward senescent cell accumulation with production of a senescence-associated secretory phenotype. Cumulatively, these changes result in bone remodeling abnormalities that over time cause net bone loss typically seen in older adults. Age-related osteoporosis is a geriatric syndrome due to the multiple etiologies that converge upon the skeleton to produce the ultimate phenotypic changes that manifest as bone fragility. Bone tissue is dynamic but with tendencies toward poor osteoblastic bone formation and relative osteoclastic bone resorption with aging. Interactions with other aging physiologic systems, such as muscle, may also confer detrimental effects on the aging skeleton. Conversely, individuals who maintain their BMD experience a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging. © 2023 American Physiological Society. Compr Physiol 13:4355-4386, 2023.

Disuse (post-mobilization) osteoporosis: literature review and clinical case series

Background. Disuse (рost-immobilization) osteoporosis is defined as secondary loss of bone mass in case of the absence or insufficient mechanical load on the skeleton. This disease can be associated with various risk factors, including long-time bed rest. The purpose of the research was to analyze modern literary data on the mechanisms of development, principles of diagnosis and treatment of disuse osteoporosis and to present own clinical data of disuse osteoporosis in the patients with multiple injuries of the skeleton in the conditions of war in Ukraine. Materials and methods. The review was based on the analysis of literature sources from the PubMed, WOS, Scopus, Google, Google Scholar, Cochrane Library databases for the years 2007–2022. The search was conducted using keywords: disuse osteoporosis, immobilization, bed rest, bone mineral density (BMD), bone remodeling, regeneration. Results. The data on the theory of the mechanostat are considered as links in the appearance of disuse osteoporosis. In conditions of immobilization, bone remodeling processes are slowing down. Histomorphometric studies confirm a decrease in trabecular bone density, thickness of the cortical layer, and an increase in its porosity. A change in bone architecture with a biphasic course is observed. Disruption of the synchronicity of remodeling processes with a decrease in the rate of osteoblastogenesis and an increase in osteoclastogenesis was noted, and the role of osteocytes as mechanosensors was emphasized. Disuse osteoporosis leads to a violation of biochemical marker of bone metabolism. Early laboratory manifestations of bed rest were recorded in the form of a violation of calcium level, an increase in bone resorption markers, while bone formation markers did not change significantly. Bone loss in disuse osteoporosis is manifested by a decrease in BMD indices. The greatest decrease was recorded in the lower extremities’ bones and the vertebrae of the lumbar spine. Modern methods of treatment of disuse osteoporosis involve the use of antiresorptive and osteoanabolic agents but clinical data are limited, which requires multicenter randomized studies. The article presents 3 clinical examples of disuse osteoporosis after gunshot fractures of the lower extremities’ bones.

Loss of Vhl alters trabecular bone loss during S. aureus osteomyelitis in a cell-specific manner.

Osteomyelitis, or bone infection, is a major complication of accidental trauma or surgical procedures involving the musculoskeletal system. Staphylococcus aureus is the most frequently isolated pathogen in osteomyelitis and triggers significant bone loss. Hypoxia-inducible factor (HIF) signaling has been implicated in antibacterial immune responses as well as bone development and repair. In this study, the impact of bone cell HIF signaling on antibacterial responses and pathologic changes in bone architecture was explored using genetic models with knockout of either Hif1a or a negative regulator of HIF-1α, Vhl. Deletion of Hif1a in osteoblast-lineage cells via Osx-Cre (Hif1aΔOB ) had no impact on bacterial clearance or pathologic changes in bone architecture in a model of post-traumatic osteomyelitis. Knockout of Vhl in osteoblast-lineage cells via Osx-Cre (VhlΔOB ) caused expected increases in trabecular bone volume per total volume (BV/TV) at baseline and, intriguingly, did not exhibit an infection-mediated decline in trabecular BV/TV, unlike control mice. Despite this phenotype, bacterial burdens were not affected by loss of Vhl. In vitro studies demonstrated that transcriptional regulation of the osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG) is altered in osteoblast-lineage cells with knockout of Vhl. After observing no impact on bacterial clearance with osteoblast-lineage conditional knockouts, a LysM-Cre model was used to generate Hif1aΔMyeloid and VhlΔMyeloid mouse models to explore the impact of myeloid cell HIF signaling. In both Hif1aΔMyeloid and VhlΔMyeloid models, bacterial clearance was not impacted. Moreover, minimal impacts on bone architecture were observed. Thus, skeletal HIF signaling was not found to impact bacterial clearance in our mouse model of post-traumatic osteomyelitis, but Vhl deletion in the osteoblast lineage was found to limit infection-mediated trabecular bone loss, possibly via altered regulation of RANKL-OPG gene transcription.

Comparison of heat production and bone architecture changes in the implant site preparation with compressive osteotomes, osseodensification technique, piezoelectric devices, and standard drills: an ex vivo study on porcine ribs

This study aimed at investigating differences in heat generation and bone architecture following four different implant site preparation techniques: compressive osteotomes, conventional drills, osseodensification (OD mode with osseodensification drills), and piezoelectric systems. Porcine rib bones were used as a model for implant surgery. Thermocouples were employed to measure temperature changes, and micro-CT to assess the bone architecture. The primary stability and insertion torque values of the implants placed in the differently prepared sites were assessed. The temperature changes were higher with Piezo. The average primary stability using the ISQ scale was the greatest for drills (76.17 ± 0.90) and the lowest for osteotomes (71.50 ± 11.09). Insertion torque was significantly higher with the osseodensification method (71.67 ± 7.99 Ncm) in comparison to drills, osteotomes, and piezo. Osteotomes showed the highest bone to implant contact percentage (39.83 ± 3.14%) and average trabecular number (2.02 ± 0.21 per mm), while drills exhibited the lowest (30.73 ± 1.65%; 1.37 ± 0.34 per mm). Total implant site bone volume was the highest with osseodensification (37.26 ± 4.13mm3) and the lowest for osteotomes (33.84 ± 3.84mm3). Statistical analysis showed a high primary stability and decrease in temperature during implant site preparation with osseodensification technique. The results support the use of osseodensification technique for implant site preparation.

Age-Dependent Changes in Bone Architecture, Patterning, and Biomechanics During Skeletal Regeneration.

Mouse digit amputation provides a useful model of bone growth after injury, in that the injury promotes intramembranous bone formation in an adult animal. The digit tip is composed of skin, nerves, blood vessels, bones, and tendons, all of which regenerate after digit tip amputation, making it a powerful model for multi-tissue regeneration. Bone integrity relies upon a balanced remodeling between bone resorption and formation, which, when disrupted, results in changes to bone architecture and biomechanics, particularly during aging. In this study, we used recently developed techniques to evaluate bone patterning differences between young and aged regenerated bone. This analysis suggests that aged mice have altered trabecular spacing and patterning and increased mineral density of the regenerated bone. To further characterize the biomechanics of regenerated bone, we measured elasticity using a micro-computed tomography image-processing method combined with nanoindentation. This analysis suggests that the regenerated bone demonstrates decreased elasticity compared with the uninjured bone, but there is no significant difference in elasticity between aged and young regenerated bone. These data highlight distinct architectural and biomechanical differences in regenerated bone in both young and aged mice and provide a new analysis tool for the digit amputation model to aid in evaluating the outcomes for potential therapeutic treatments to promote regeneration.

A Split Mouth Study on Crestal Bone Architectural Changes by Flapped and Flapless Implant Surgical Procedures

Background: Rehabilitations by dental implants have often been utilized as an efficient procedure for restoring missing teeth. For implant placement two types of surgical methods are well documented. Conventional surgical approach involves raising a mucoperiosteal flap to gain access and see the underlying alveolar bone, instead there is this procedure which does not involve the reflection of the flap. Both the techniques are known to have their individual benefits and shortcomings. The present study was aimed to evaluate the longitudinal comparison and evaluation of hard tissue changes around endosseous implants placed using flapped as well as flapless surgical procedures in mandibular first molar region.
 Materials and Methods: A total of 10 healthy patients with bilateral mandibular first molar were involved in the study and 20 endosseous implants were inserted (10 in each group). Radiographic assessment was done for deviations in the marginal bone levels on both mesial and distal side and their average value was calculated at 1 month, and 3 months. All these parameters were statistically analyzed using the paired Student t test, and two-way ANOVA test and were considered to be significant if the p value was ≤ 0.05.
 Results: During the 3 months observation period, the change in crestal bone height around the implants placed by flapless and flap surgery were statistically significant. The flapless group showed less reduction in the crestal bone height compared to the flap group.
 Conclusion: Both flap and the flapless techniques of endosseous implant placement had statistically significant effect on peri-implant bone loss over the 3 month period.

CURRENT TRENDS IN BONE AUGMENTATION DURING DENTAL IMPLANTATION IN PATIENTS WITH PARODONTAL PATHOLOGY AND JAW BONE ATROPHY (LITERATURE REVIEW)

Today, despite the progress made in dental implantology, the problem of rehabilitation of patients with significant bone atrophy in parodontal diseases has not been fully studied.
 The study aims to review the current views of various authors on the aetiology and treatment of parodontal diseases, which caused multiple tooth loss and bone atrophy in patients with occlusal pathology, based on the literature sources of scientific and medical information.
 Object and methods of study. Analytical study of scientific and medical literature on the treatment of multiple and partial tooth loss in patients with parodontal diseases in bone atrophy with impaired jaw relationships and orthopaedic rehabilitation using dental implantation and methods of bone augmentation of the mandible and maxilla.
 The use of implants in orthopaedic treatment expands the possibilities of using fixed prostheses, satisfying patients functionally and aesthetically. In case when the preservation of teeth becomes impossible or impractical to ensure proper treatment of the patient, they can be removed and replaced with dentures on dental implants.
 According to Misch C. [6], the masticatory load, which is exerted on the bone tissue of the jaws by an implant, increases the density of the bone structure. When teeth are lost due to parodontitis, there is atrophy of the alveolar ridge and a change in the structure of bone tissue, which is characterized by an increase in the porosity of the cancellous bone [4;5;7]. Sufficient bone volume and density in the area of the planned implantation are the main and important parameters for achieving normalized primary implant stabilization [11]. Partial and complete loss of teeth, as well as parodontal diseases, are always accompanied by the bone tissue of alveolar bone tissue of varying severity [1;4;5;13]. Signs of parodontal diseases in dentition defects are always more pronounced than in intact dental arch. The disease progresses rapidly, the dentition is destroyed if appropriate occlusal therapy is not performed [13;14]. Systemic factors and comorbidities in patients also play a significant role in reducing the bone volume of the jaws.
 The relationship between decreased bone density and age-related hormonal changes in women, as well as at the gender level, has been studied. Thus, women have changes in bone architecture and less dense arrangement of trabeculae in the jawbones than men [15].Bone tissue has a distinguishing feature – loss of multiple teeth or parodontal diseases lead to a redistribution of functional load, which causes its resorption [7;20]. In this regard, tooth extraction inevitably leads to a decrease in bone volume. The success of dental implantation on the maxilla became partially possible due to the introduction of sinus lifting with the use of osteoplastic materials [12;20;21]. According to some scientists[21], the autogenous bone graft is the gold standard in regenerative processes due to its osteoinductive, osteoconductive, and osteointegration properties, which are necessary for the restoration of lost bone tissue.
 The use of dentin in human teeth as an autograft was first described in a clinical case report in 2003 [23]. In recent experiments, these materials have proven to be a real alternative to the bone graft. Thanks to the work of a group of researchers [23;24], significant efforts were made in the basic and clinical study to find the best bone graft material for osseointegration of implants in the maxillary sinus. The autogenous dentin graft (AutoBT; Korea Tooth Bank, Seoul, Korea) was first developed in 2008, and several clinical studies have praised the use of AutoBT in the sinus compared to other grafts.
 Given the current development of advanced technologies in dental implantation, dentists use navigation templates in their practice, which are made using CAD CAM technology to improve the quality of care for patients who have indications for dental implantation. New diagnostic approaches allow us to virtually plan, simplify, and speed up surgery, to ensure accuracy. Thanks to this technology, dentists optimize the location of dental implants, taking into account the difficult conditions specific to patients with parodontal pathology.

The Effect of Inflammation on Bone.

Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.

Lifelong Excess in GH Elicits Sexually Dimorphic Effects on Skeletal Morphology and Bone Mechanical Properties.

Excess in growth hormone (GH) levels, seen in patients with acromegaly, is associated with increases in fractures. This happens despite wider bones and independent of bone mineral density. We used the bovine GH (bGH) transgenic mice, which show constitutive excess in GH and insulin-like growth factor 1 (IGF-1) in serum and tissues, to study how lifelong increases in GH and IGF-1 affect skeletal integrity. Additionally, we crossed the acid labile subunit (ALS) null (ALSKO) to the bGH mice to reduce serum IGF-1 levels. Our findings indicate sexually dimorphic effects of GH on cortical and trabecular bone. Male bGH mice showed enlarged cortical diameters, but with marrow cavity expansion and thin cortices as well as increased vascular porosity that were associated with reductions in diaphyseal strength and stiffness. In contrast, female bGH mice presented with significantly smaller-diameter diaphysis, with greater cortical bone thickness and with a slightly reduced tissue elastic modulus (by microindentation), ultimately resulting in overall stronger, stiffer bones. We found increases in C-terminal telopeptide of type 1 collagen and procollagen type 1N propeptide in serum, independent of circulating IGF-1 levels, indicating increased bone remodeling with excess GH. Sexual dimorphism in response to excess GH was also observed in the trabecular bone compartment, particularly at the femur distal metaphysis. Female bGH mice preserved their trabecular architecture during aging, whereas trabecular bone volume in male bGH mice significantly reduced and was associated with thinning of the trabeculae. We conclude that pathological excess in GH results in sexually dimorphic changes in bone architecture and gains in bone mass that affect whole-bone mechanical properties, as well as sex-specific differences in bone material properties. © 2022 American Society for Bone and Mineral Research (ASBMR).

Associations of Muscle Size and Density With Proximal Femur Bone in a Community Dwelling Older Population.

Background and Purpose: Muscle weakness and bone fragility are both associated with hip fracture. In general, muscle contractions create forces to the bone, and bone strength adapts to mechanical loading through changes in bone architecture and mass. However, the relationship between impairment of muscle and bone function remain unclear. In particular, the associations of muscle with properties of proximal femur cortical and trabecular bone are still not well understood. The aim of this study was to explore the associations of hip/thigh muscle density (CT attenuation value in Hounsfield units) and size with cortical and trabecular bone mineral density (BMD) of the proximal femur.Materials and Methods: Three-dimensional quantitative computed tomography (QCT) imaging of the lumber, hip and mid-thigh was performed in a total of 301 participants (mean age 68.4 ± 6.1 years, 194 women and 107 men) to derive areal BMD (aBMD) and volumetric BMD (vBMD). Handgrip strength (HGS) and the Timed Up and Go (TUG) test were also performed. From the CT images, cross-sectional area (CSA), and density were determined for the gluteus maximus muscle (G.MaxM), trunk muscle at the vertebrae L2 level, and mid-thigh muscle. Multivariate generalized linear models were applied to assess associations.Results: Total hip (TH) aBMD was associated significantly with G.MaxM CSA (men: P = 0.042; women: P < 0.001) and density (men: P = 0.012; women: P = 0.043). In women, 0.035 cm2 of mid-thigh CSA (95% CI, 0.014–0.057; P = 0.002) increased per SD increase in TH aBMD, but this significance was not observed in men (P = 0.095). Trunk muscle density and CSA were not associated with proximal femur BMD. The associations of hip/thigh muscle parameters with femoral neck BMD were weaker than those with trochanter and intertrochanter BMD. Furthermore, compared to muscle density, muscle CSA showed better associations with vBMD. G.MaxM CSA was associated with trochanter (TR) Cort. vBMD in men (β, 19.898; 95% CI, 0.924–38.871; P = 0.040) and in women (β, 15.426; 95% CI, 0.893–29.958; P = 0.038). Handgrip strength was only associated with TR aBMD (β, 0.038; 95% CI, 0.006–0.070; P = 0.019) and intertrochanter aBMD (β, 0.049; 95% CI, 0.009–0.090; P = 0.016) in men.Conclusions: We observed positive associations of the gluteus and thigh muscle size with proximal femur volumetric BMD. Specifically, the gluteus maximus muscle CSA was associated with trochanter cortical vBMD in both men and women.

Bone Mass, Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis.

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro-finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = -0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = -1.23, p = .02). HOA was associated with lower failure load (-514 N; 95%CI, -1018 to -9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Associations of Sex Steroids With Changes in Calcaneal Quantitative Ultrasound Measurements: A Longitudinal Study in Chinese Male Adolescents

This 2-year longitudinal study aimed to detect the associations of sex steroids, sex hormone-binding globulin with bone parameters and the changes thereof in Chinese male adolescents. A total of 642 male students aged 12–16 years from a secondary school in Jiangmen, China, were included. Total testosterone (T), total oestradiol (E2), and sex hormone-binding globulin were measured by chemiluminescence immunoassay. The bioavailable T (BioT) and E2 (BioE2) were calculated. The speed of sound, broadband ultrasound attenuation, and stiffness index of the right heel were measured by Sahara Clinical Bone Sonometer at both baseline and 2-year follow-up. The confounding effects of age, height, weight, pubertal stage, physical activity, energy-adjusted dietary calcium intake, and dietary vitamin D intake were adjusted. The baseline value of each bone parameter was also adjusted in the longitudinal analysis. Results showed that total T and BioT were positively associated with bone parameters and changes in them (β = 0.076–0.115, p < 0.05). A threshold effect of BioT on broadband ultrasound attenuation, stiffness index and their changes were also observed. Positive associations between BioT and bone mass gain were observed only in individuals with BioT levels <240.0 ng/dl (β = 0.088–0.131, p < 0.05). Moreover, total E2 or BioE2 were found to be inversely associated with speed of sound and its change (β = −0.109 to –0.077, p < 0.05). This study supported that in Chinese male adolescents, serum T was a positive predictor for bone formation with a threshold effect, and E2 could have influence on the changes in bone architecture during puberty. These findings may improve the understanding of the effects of sex steroids on the acceleration of bone formation in male adolescents and provide useful information for the prediction model establishment of peak bone mass.

Subchondral trabecular bone integrity changes following ACL injury and reconstruction: a cohort study with a nested, matched case-control analysis

There is limited information regarding changes in bone architecture following anterior cruciate ligament (ACL) injury. The objective of this study was to evaluate differences in tibial fractal signature in the medial and lateral compartments following ACL injury and describe how these values change following ACL-reconstruction and return to activity. This was a prospective cohort study with a nested case-control analysis. ACL-injured subjects and matched controls were evaluated at pre-surgical baseline and post ACL reconstruction follow-up at a mean of 46 months. Serial Fractal Dimensions (FD) of tibial subchondral bone architecture were calculated in medial and lateral regions of interest in the horizontal and vertical dimensions. In the medial and lateral compartments, there were significant differences in the vertical FD signature for ACL-injured subjects at final follow-up, when compared to the contralateral healthy tibia (medial P<0.0001; lateral P<0.0001) and the control group (medial P=0.01; lateral P<0.0001). Similarly, in the lateral compartment, there were significant differences in the horizontal FD profile for ACL-injured subjects at final follow-up, when compared to the contralateral healthy tibia (P=0.003) and the controls (P<0.0001). There were no significant side-to-side differences in FDs among healthy control subjects in the medial or lateral compartments at baseline or final follow-up. At 46-month follow-up, FD profiles are significantly different, and show an overall lower FD signature, for ACL-injured knees when compared to the contralateral healthy knee and uninjured controls. Additionally, this study provided the first side-to-side symmetry data of medial and lateral FD values in healthy controls.