Periosteal Bone Apposition Research Articles

Chicken eggshell powder more effectively alleviates bone loss comparted to inorganic calcium carbonate: an animal study performed on ovariectomized rats.

This study aimed to evaluate the effects of chicken eggshell powder rich in calcium and the inorganic form of calcium carbonate on osteoporotic bone structure using an animal model of ovariectomized rats. Animals were divided into four groups: sham-operated rats (SHAM group); ovariectomized rats untreated (OVX group); OVX rats treated with eggshell powder (Biomin H® OVX + ECa group; total Ca content 1.5%); and OVX rats receiving inorganic calcium carbonate (calcium carbonate precipitated, total Ca content 1.5%; OVX + ICa group) during 8 weeks. Ovariectomy increased total body weight, plasma alkaline phosphatase activity, cortical bone thickness, periosteal bone apposition, and considerably worsened the trabecular bone microarchitecture. Calcium supplementation in both OVX + ECa and OVX + ICa groups elevated blood supply in the cortical bone when compared to OVX rats. Treatment with eggshell powder, unlike the OVX + ICa group, significantly lowered bone resorption, increased plasma calcium level, relative volume of trabecular bone, and secondary osteon population density, which together contributes to the enhanced bone strength. In addition, sizes of Haversian canals and secondary osteons in OVX + ECa group reached the values of SHAM group. Our results suggest that chicken eggshell powder more effectively ameliorates bone loss in ovariectomized rats than precipitated calcium carbonate.

The effect of low intensity pulsed ultrasound on mandibular condylar growth in young adult rats

There is a need for more effective methods to enhance mandibular growth in young adults with mandibular deficiency. Previous studies suggest that low intensity pulsed ultrasound (LIPUS) can enhance mandibular growth in growing individuals. This study aimed to evaluate the potential growth changes of the mandible following 4-week LIPUS application in young adult rats. Nineteen ≈120-day-old female rats were allocated to experimental (n = 10) and control (n = 9) groups. The animals in the experimental group were treated with LIPUS to their temporomandibular joints (TMJs) bilaterally, 20 min each day for 28 consecutive days. Animals were then euthanized; gross morphological evaluation was performed on 2D photographs and 3D virtual models of hemi-mandibles, and microstructural assessment was done for the mandibular condyle (MC). Evaluation of mineralization and microarchitecture properties of subchondral cancellous bone was performed by micro-computed tomography (μCT) scanning. Qualitative and histomorphometric analysis was done on condylar cartilage and subchondral bone following Alcian Blue/PAS and Goldner's Trichrome staining. Vital flourochrome (calcein green) labeling was also utilized to determine the amount of endochondral bone growth. Gross morphological evaluations showed a slight statistically non-significant increase especially in the main condylar growth direction in the LIPUS group. Moreover, 3D evaluation depicted an enhanced periosteal bone apposition at the site of LIPUS application. Microstructural analysis revealed that LIPUS stimulates both chondrogenesis and osteogenesis and enhances endochondral bone formation in young adult rat MC. Furthermore, the effect of LIPUS on osteogenic cells of subchondral cancellous bone was notable. To conclude, LIPUS can enhance young adult rats' MC residual growth potential.

Bee Bread Can Alleviate Lipid Abnormalities and Impaired Bone Morphology in Obese Zucker Diabetic Rats.

This study examined for the first time whether bee bread (BB, consisting of monofloral rape bee pollen) could alleviate lipid derangements and reduced bone quality in Zucker diabetic fatty (ZDF) rats, which are considered an appropriate animal model for type 2 diabetes mellitus (T2DM) investigation. Adult ZDF rats were segregated into four groups: lean non-diabetic rats (L group), obese diabetic rats untreated (C group), and those treated with the BB at two doses (500 and 700 mg/kg body weight, respectively, B1 and B2 groups) for 10 weeks. Significantly reduced levels of total cholesterol and triglyceride were recorded in the B2 group versus the C group. In both BB-treated groups, significantly increased relative volume of trabecular bone and trabecular thickness, enhanced density of secondary osteons, accelerated periosteal bone apposition, and improved blood flow were observed. A positive effect of higher dose of BB on femoral weight and cortical bone thickness was also demonstrated. Our results suggest a promising potential of BB to ameliorate T2DM-related complications associated with lipid and bone damages.

Cornelian Cherry Pulp Has Beneficial Impact on Dyslipidemia and Reduced Bone Quality in Zucker Diabetic Fatty Rats.

Simple SummaryFruits of Cornelian cherry (Cornus mas L.) are often used as an antidiabetic supplement mainly due to their hypoglycemic properties. A very important aspect and secondary complication of type 2 diabetes mellitus (T2DM) represents diabetic bone disease. In our study, the impacts of Cornus mas pulp on lipid profile and bone quality parameters were evaluated in Zucker diabetic fatty (ZDF) rats as a well-matched T2DM animal model. We demonstrated, for the first time, that Cornelian cherry pulp could be used as a potential therapeutic agent to alleviate T2DM-reduced bone quality and impaired bone health. Moreover, the hypolipidemic effect of this fruit was also confirmed in our study.Cornelian cherry (Cornus mas L.) is a medicinal plant with a range of biological features. It is often used as a nutritional supplement in the treatment of diabetes mellitus. Our study was aimed to first investigate the effects of Cornelian cherry pulp on bone quality parameters in Zucker diabetic fatty (ZDF) rats. Moreover, lipid-lowering properties of this fruit were also evaluated. Adult rats (n = 28) were assigned into four groups of seven individuals each: L group (non-diabetic lean rats), C group (diabetic obese rats), and E1 and E2 groups (diabetic obese rats receiving 500 and 1000 mg/kg body weight of Cornelian cherry pulp, respectively, for 10 weeks). Significantly lower levels of triglyceride, total cholesterol and alkaline phosphatase activity were determined in the E2 group versus the C group. A higher dose of Cornus mas also had a beneficial impact on femoral weight, cortical bone thickness, relative volume of trabecular bone and trabecular thickness. We observed elevated density of Haversian systems and accelerated periosteal bone apposition in both treated groups (E1 and E2). Our results clearly demonstrate that Cornelian cherry pulp has a favorable effect on lipid disorder and impaired bone quality consistent with type 2 diabetes mellitus in a suitable animal model.

The effects of eggshell calcium (Biomin H® ) and its combinations with alfacalcidol (1α-hydroxyvitamin D3) and menaquinone-7 (vitamin K2) on ovariectomy-induced bone loss in a rat model of osteoporosis.

The purpose of this study was to investigate the impact of eggshell calcium (Biomin H® dietary supplement) and its combinations with alfacalcidol (1α-hydroxyvitamin D3 ) and menaquinone-7 (vitamin K2 ) on ovariectomy-induced bone loss in rats. Adult female rats (n=48) were divided into 6 groups of 8 individuals each: sham-operated rats (SHAM); ovariectomized (OVX) rats untreated; OVX rats treated with Biomin H® (BIO); OVX rats simultaneously receiving Biomin H® , vitamin D3 (BIO+D3 ); OVX rats simultaneously treated with Biomin H® , vitamin K2 (BIO+K2 ) and OVX rats treated with Biomin H® , vitamin D3 , vitamin K2 (BIO+D3 +K2 ) during 8weeks. Biochemical parameters, bone mineral density (BMD), bone mineral content (BMC) and femoral bone microstructure were determined. Plasma calcium and phosphate were increased in BIO+D3 and BIO+D3 +K2 groups as compared to OVX. Alkaline phosphatase was elevated in OVX, BIO versus SHAM, BIO+D3 +K2 groups. When compared to OVX group, decreased urine deoxypyridinoline was observed in all treated groups and femoral BMD, BMC were higher in BIO, BIO+D3 , BIO+D3 +K2 groups. The BIO+K2 rats had similar densitometrical values than OVX individuals. Microcomputed tomography revealed increased trabecular relative bone volume (due to an increase in trabecular number) in BIO+D3 , BIO+D3 +K2 as compared to OVX. The higher relative bone volume in BIO+D3 , BIO+D3 +K2 groups was also accompanied by an increase in bone surface. In the cortical bone, an enhanced periosteal bone apposition was identified in BIO, BIO+D3 , BIO+K2 , BIO+D3 +K2 groups. The rats from BIO+D3 +K2 group had a higher area of primary osteon's vascular canals. In BIO+D3 , BIO+K2 , BIO+D3 +K2 groups, an increased area of secondary osteons was determined in comparison with OVX. Our results indicate the beneficial effect of triple application of Biomin H® , vitamin D3 , vitamin K2 , as well as simultaneous administration of Biomin H® , vitamin D3 on the inhibition of ovariectomy-induced bone loss in a rat model of osteoporosis.

Micro-anatomical structure of the first spine of the dorsal fin of Atlantic bluefin tuna, Thunnus thynnus (Osteichthyes: Scombridae)

The first spine of the first dorsal fin (FS) of the Atlantic bluefin tuna (ABFT), Thunnus thynnus, is customarily used in age determination research because its transverse sections display well-defined growth marks. In this paper the FS structure was studied to explain its known dramatic age- and season-related morphological modifications, which are evidently caused by bone remodeling. Cross sections of samples from six adult ABFT were in part decalcified to be stained with histological, histochemical and immunohistochemical methods, and in part embedded in methyl-methacrylate to be either observed under a linear polarized light or microradiographed. FS showed an external compact bone zone and an inner trabecular bone zone. The compact bone zone consisted of an outer non-osteonic primary bone layer (C1) and an inner osteonic bone layer (C2). C1 was in turn characterized by alternate translucent and opaque bands. Evidence of spine bone remodeling was shown by the presence of osteoclasts and osteoblasts as well as by tartrate-resistant acid phosphatase (TRAP) positive bands at the boundary between old and newly formed bone. The examination of plain, i.e. not-fixed and not-decalcified, FS from 28 ABFT showed that the average thickness of C1 remained fairly constant during fish growth, whereas C2 increased significantly, indicating that the periosteal primary bone apposition is counterbalanced by the parallel bone remodeling occurring inside the compact bone zone. The present study revealed the structure of the ABFT FS and the pattern of its bone remodeling. Both of them underlay phenomena, never examined in detail before, such as the appearance followed by the progressive disappearance of growth bands.

A POSITIVE DOSE-RESPONSE OF QUERCETIN ON COMPACT BONE MICROSTRUCTURE OF MALE RABBITS

Quercetin is one of the most widely distributed flavonoids in plants which should have a broad range of significant health promoting properties. Its effect on bone microstructure of males has not been sufficiently investigated. Therefore, our study was aimed to determine the impact of quercetin on femoral bone microstructure in 5-month-old male rabbits. Nine rabbits were intramuscularly injected with following doses of quercetin: 10 μg/kg body weight (bw) (E1 group; n=3), 100 μg/kg bw (E2 group; n=3) and 1000 μg/kg bw (E3 group; n=3) for 90 days, 3 times per week. Three rabbits without quercetin administration served as a control group. An accelerated bone resorption at the endosteal surface and intensive periosteal bone apposition were observed in all rabbits administered quercetin. However, the most evident changes such as a thicker layer of primary vascular longitudinal bone tissue under periosteum and a lower density of secondary osteons were identified in males from the E3 group. Morphometrical evaluations of the compact bone showed significantly decreased sizes of primary osteons’ vascular canals and secondary osteons in rabbits exposed to the highest dose of quercetin. Sizes of secondary osteons were also lower in males from the E2 group. Our results demonstrate that quercetin has a positive dose-response on compact bone microstructure in male rabbits.

Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor.

Osteocytes integrate the responses of bone to mechanical and hormonal stimuli by poorly understood mechanisms. We report here that mice with conditional deletion of the parathyroid hormone (PTH) receptor 1 (Pth1r) in dentin matrix protein 1 (DMP1)-8kb-expressing cells (cKO) exhibit a modest decrease in bone resorption leading to a mild increase in cancellous bone without changes in cortical bone. However, bone resorption in response to endogenous chronic elevation of PTH in growing or adult cKO mice induced by a low calcium diet remained intact, because the increased bone remodeling and bone loss was indistinguishable from that exhibited by control littermates. In contrast, the bone gain and increased bone formation in cancellous and cortical bone induced by daily injections of PTH and the periosteal bone apposition induced by axial ulna loading were markedly reduced in cKO mice compared to controls. Remarkably, however, wild-type (WT) control littermates and transgenic mice overexpressing SOST injected daily with PTH exhibit similar activation of Wnt/β-catenin signaling, increased bone formation, and cancellous and cortical bone gain. Taken together, these findings demonstrate that Pth1r in DMP1-8kb-expressing cells is required to maintain basal levels of bone resorption but is dispensable for the catabolic action of chronic PTH elevation; and it is essential for the anabolic actions of daily PTH injections and mechanical loading. However, downregulation of Sost/sclerostin, previously shown to be required for bone anabolism induced by mechanical loading, is not required for PTH-induced bone gain, showing that other mechanisms downstream of the Pth1r in DMP1-8kb-expressing cells are responsible for the hormonal effect. © 2016 American Society for Bone and Mineral Research.

Alterations of Bone Density, Microstructure, and Strength of the Distal Radius in Male Patients With Rheumatoid Arthritis: A Case-Control Study With HR-pQCT

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation.

Atomic Force Microscopy Characterization of the External Cortical Bone Surface in Young and Elderly Women: Potential Nanostructural Traces of Periosteal Bone Apposition During Aging

On the basis of the suggestion that bone nanostructure bears “tissue age” information and may reflect surface deposition/modification processes, we performed nanoscale characterization of the external cortical bone surface at the femoral neck in women using atomic force microscopy (AFM). The specific aims were to assess age-related differences in bone nanostructure and explore the existence of nanostructural traces of potential bone apposition at this surface. Our findings revealed that the external cortical surface represents a continuous phase composed of densely packed mineral grains. Although the grains varied in size and shape, there was a domination of small grains indicative of freshly deposited bone (mean grain size: young, 35 nm; old, 37 nm; p > 0.05). Advanced quantitative analysis of surface morphological patterns revealed comparable roughness and complexity of the surface, suggesting a similar rate of mineral particle deposition at the surface in both groups. Calcium/phosphorus ratio, a measure of bone tissue age, was within the same range in both groups. In summary, our AFM analyses showed consistent nanostructural and compositional bone features, suggesting existence of new bone at the periosteal bone surface in both young and elderly women. Considering observed age-related increase in the neck diameter, AFM findings may support the theory of continuous bone apposition at the periosteal surface.

Cortical remodeling during menopause, rheumatoid arthritis, glucocorticoid and bisphosphonate therapy

Bone mass, bone geometry and its changes are based on trabecular and cortical bone remodeling. Whereas the effects of estrogen loss, rheumatoid arthritis (RA), glucocorticoid (GC) and bisphosphonate (BP) on trabecular bone remodeling have been well described, the effects of these conditions on the cortical bone geometry are less known. The present review will report current knowledge on the effects of RA, GC and BP on cortical bone geometry and its clinical relevance. Estrogen deficiency, RA and systemic GC lead to enhanced endosteal bone resorption. While in estrogen deficiency and under GC therapy endosteal resorption is insufficiently compensated by periosteal apposition, RA is associated with some periosteal bone apposition resulting in a maintained load-bearing capacity and stiffness. In contrast, BP treatment leads to filling of endosteal bone cavities at the epiphysis; however, periosteal apposition at the bone shaft seems to be suppressed. In summary, estrogen loss, RA and GC show similar effects on endosteal bone remodeling with an increase in bone resorption, whereas their effect on periosteal bone remodeling may differ. Despite over 50 years of GC therapy and over 25 years of PB therapy, there is still need for better understanding of the skeletal effects of these drugs as well as of inflammatory disease such as RA on cortical bone remodeling.

Periapical Disease and Bisphosphonates Induce Osteonecrosis of the Jaws in Mice

Osteonecrosis of the jaw (ONJ) is a well-recognized complication of antiresorptive medications, such as bisphosphonates (BPs). Although ONJ is most common after tooth extractions in patients receiving high-dose BPs, many patients do not experience oral trauma. Animal models using tooth extractions and high BP doses recapitulate several clinical, radiographic, and histologic findings of ONJ. We and others have reported on rat models of ONJ using experimental dental disease in the absence of tooth extraction. These models emphasize the importance of dental infection/inflammation for ONJ development. Here, we extend our original report in the rat, and present a mouse model of ONJ in the presence of dental disease. Mice were injected with high dose zoledronic acid and pulpal exposure of mandibular molars was performed to induce periapical disease. After 8 weeks, quantitative and qualitative radiographic and histologic analyses of mouse mandibles were done. Periapical lesions were larger in vehicle-treated versus BP-treated mice. Importantly, radiographic features resembling clinical ONJ, including thickening of the lamina dura, periosteal bone deposition, and increased trabecular density, were seen in the drilled site of BP-treated animals. Histologically, osteonecrosis, periosteal thickening, periosteal bone apposition, epithelial migration, and bone exposure were present in the BP-treated animals in the presence of periapical disease. No difference in tartrate-resistant acid phosphatase (TRAP)+ cell numbers was observed, but round, detached, and removed from the bone surface cells were present in BP-treated animals. Although 88% of the BP-treated animals showed areas of osteonecrosis in the dental disease site, only 33% developed bone exposure, suggesting that osteonecrosis precedes bone exposure. Our data further emphasize the importance of dental disease in ONJ development, provide qualitative and quantitative measures of ONJ, and present a novel mouse ONJ model in the absence of tooth extraction that should be useful in further exploring ONJ pathophysiological mechanisms.

Hypertrophic osteopathy associated with a bronchial foreign body (grass awn) in a dog: a case report

A five-year-old dog was referred with a five-month history of lethargy, decreased appetite, cough and intermittent forelimb lameness. Radiographs revealed an intra-thoracic lesion and a marked periosteal bone apposition of the second digit on the left forelimb. As it was palisading and circumferential, the latter appeared typical of hypertrophic osteopathy (HO). A grass awn in a sub-lobar ramification of the right caudal bronchus was identified and removed by bronchoscopy. At three months follow-up, the digit appeared clinically normal. On radiographs the periosteal bone reaction had decreased, indicative of resolving hypertrophic osteopathy. Thoracic radiographs showed no abnormalities five months after foreign body removal and the bone lesion on the digit had disappeared. Successful treatment of the pulmonary foreign body abscess led to spontaneous regression of HO and eventually to complete resolution of clinical signs. To the authors’ knowledge, this is the first reported case of HO secondary to a bronchial-pulmonary grass an abscess.

Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices

Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus (DM) and peripheral neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture. We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density (BMD) and geometric strength indices using volumetric quantitative computed tomography. Twenty individuals with DM+PN were compared to twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals. Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM+PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet. There was a non-significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM+PN and CN subjects despite the CN group's significantly lower BMD. Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively. In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury rather than increased fracture resistance. Future research using these techniques will aid further understanding of the inflammation-mediated bony changes associated with development and progression of CN and other diseases.

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross-sectional study of 66 middle-aged female RA patients and 66 age-matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were -5.7% to -23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR-pQCT provides new insight into inflammation-associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity.

Bone and hypopituitarism: not only a mass issue

Bone and hypopituitarism: not only a mass issue

Lactation is associated with greater maternal bone size and bone strength later in life

The association between lactation and bone size and strength was studied in 145 women 16 to 20 years after their last parturition. Longer cumulative duration of lactation was associated with larger bone size and strength later in life. Pregnancy and lactation have no permanent negative effect on maternal bone mineral density but may positively affect bone structure in the long term. We hypothesized that long lactation promotes periosteal bone apposition and hence increasing maternal bone strength. Body composition, bone area, bone mineral content, and areal bone mineral density of whole body and left proximal femur were assessed using DXA, and cross-sectional area and volumetric bone mineral density of the left tibia shaft were measured by pQCT in 145 women (mean age 48 years, range 36-60 years) 16 to 20 years after their last parturition. Hip (HSI) and tibia strength indexes (TBSI) were calculated. Medical history and lifestyle factors including breastfeeding patterns and durations were collected via a self-administered questionnaire. Weight change during each pregnancy was collected from personal maternity tracking records. Sixteen to 20 years after the last parturition, women who had breastfed in total more than 33 months in their life, regardless of the number of children, had greater bone strength estimates of the hip (HSI = 1.92 vs. 1.61) and the tibia (TBSI = 5,507 vs. 4,705) owing to their greater bone size than mothers who had breastfed less than 12 months (p < 0.05 for all). The differences in bone strength estimates were independent of body height and weight, menopause status, use of hormone replacement therapy, and present leisure time physical activity level. Breastfeeding is beneficial to maternal bone strength in the long run.

Hypothalamic Suppression during Adolescence Varies by Bone Envelope

The purposes of this study were to suppress estradiol levels in adolescent (postpubertal rats) using gonadotropin-releasing hormone antagonist (GnRH-a) injections and to determine the changes in bone structure and mechanical strength. In an Institutional Animal Care and Use Committee-approved study, female rats at 23 d of age were assigned to a baseline group (BL65; n = 10) sacrificed on day 65, a control group (Control; n = 15) sacrificed on day 90, or an experimental group (AMEN; n = 9) sacrificed on day 90 that received daily injections of GnRH-a for a 25-d period from 65 to 90 d of age (2.5 mg·kg(-1) per dose). Body weights were similar on day 65; however, the AMEN group was significantly heavier than the Control group (17%, P = 0.001) on day 90. In the AMEN rats relative to the Control group, plasma estradiol levels were reduced by 36% (P = 0.0001) and plasma insulin-like growth factor 1 levels were 24% higher (P = 0.003). In the femur, there was no change in periosteal bone apposition or total cross-sectional area. The marrow area increased by 13.7% (P = 0.05) resulting in a 7.8% decrease in relative cortical area (P = 0.012), and endocortical bone formation rate increased by 39.4% (P = 0.04). Trabecular volume and number decreased by 51.5% (P = 0.0003) and 49.5% (P = 0.0003), respectively. The absolute peak moments of the tibiae and femurs were unchanged in the AMEN group relative to the Control group, but these were reduced by 8.8% (P = 0.03) and 7.5% (P = 0.09), respectively, when normalized by body weight. Suppression of estradiol by 25 d of GnRH-a administration to 65-d-old (postpubertal) rats reduced trabecular volume and number by about 50%, increased endocortical bone turnover, and reduced relative cortical thickness without changing tibial and femoral total area. These changes in bone structure were associated with no change in absolute mechanical strength possibly because of increases in body weight or in insulin-like growth factor 1 concentrations.

Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling

Connexin43 (Cx43) has an important role in skeletal homeostasis, and Cx43 gene (Gja1) mutations have been linked to oculodentodigital dysplasia (ODDD), a human disorder characterized by prominent skeletal abnormalities. To determine the function of Cx43 at early steps of osteogenesis and its role in the ODDD skeletal phenotype, we have used the Dermo1 promoter to drive Gja1 ablation or induce an ODDD mutation in the chondro-osteogenic linage. Both Gja1 null and ODDD mutant mice develop age-related osteopenia, primarily due to a progressive enlargement of the medullary cavity and cortical thinning. This phenotype is the consequence of a high bone turnover state, with increased endocortical osteoclast-mediated bone resorption and increased periosteal bone apposition. Increased bone resorption is a noncell autonomous defect, caused by exuberant stimulation of osteoclastogenesis by Cx43-deficient bone marrow stromal cells, via decreased Opg production. The latter is part of a broad defect in osteoblast differentiation and function, which also results in abnormal structural and material properties of bone leading to decreased resistance to mechanical load. Thus Cx43 in osteogenic cells is a critical regulator of both arms of the bone remodeling cycle, its absence causing structural changes remindful of aged or disused bone.

An approach to quantifying bone overloading and hypertrophy with applications to multiple experimental studies

Many studies have investigated mechanically induced bone formation in mice and rats by applying loads to the long bones, and measuring changes in periosteal cortical bone apposition rates. However, the results are difficult to compare among each other because the loading schemes are generally different. The purpose of the present study was to develop a theoretical framework for evaluating the mechanical stimulus based on the bone daily strain stimulus, which is a function of loading cycles and bone strains. The daily strain stimulus would act as a single unifying parameter for directly comparing data from existing in vivo experiments, and is applied here to twenty previous rat and mouse studies. To calculate the daily strain stimulus, we determined the periosteal daily strain stimulus necessary for bone maintenance (ξperi,0) and the strain-cycle weighting exponent (m). In the first approach, we applied data from Rubin and Lanyon's bone maintenance studies. We calculated ξperi,0 to be 2793 microstrain/day, and m to be 4.5. In the second approach, we used Fritton et al. 's strain gage recordings to calculate ξperi,0 to be 1496 microstrain/day, and used an m value of 11.88, equal to human bone compressive fatigue properties. Fatigue data provided physiological relevance, and was useful for applying an established remodeling theory to in vivo studies. For both approaches, ξperi,0 was below the fracture level. We then analyzed the applied strains, cycles, and periosteal bone apposition rates from the previous studies. The range of daily strain stimuli calculated using the first approach was much larger than the range using the second approach (2793–17312 microstrain/day compared to 1496–7681 microstrain/day). None of the studies applied a daily strain stimulus above the complete fatigue failure level, but some studies applied loading that could result in major fatigue microdamage. Bone apposition rates generally increased with increasing daily strain stimulus, which was consistent with previous theoretical models. The results suggest that the daily strain stimulus may be a reasonable first approximation for predicting bone apposition rates in a consistent manner. The use of the daily strain stimulus may be helpful for improving the design of future bone loading studies.