Slow Bone Turnover Research Articles

Histological analysis on tissues around orthodontically intruded maxillary molars using temporary anchorage devices: A case report

Before progress was recently made in the application of temporary anchorage devices (TADs) in bio-mechanical design, orthodontists were rarely able to intrude molars to reduce upper posterior dental height (UPDH). However, TADs are now widely used to intrude molars to flatten the occlusal plane or induce counterclockwise rotation of the mandible. Previous studies involving clinical or animal histological evaluation on changes in periodontal conditions after molar intrusion have been reported, however, studies involving human histology are scarce. This case was a Class I malocclusion with a high mandibular plane angle. Upper molar intrusion with TADs was performed to reduce UPDH, which led to counterclockwise rotation of the mandible. After 5 months of upper molar intrusion, shortened clinical crowns were noticed, which caused difficulties in oral hygiene and hindered orthodontic tooth movement. The mid-treatment cone-beam computed tomography revealed redundant bone physically interfering with buccal attachment and osseous resective surgeries were followed. During the surgeries, bilateral mini screws were removed and bulging alveolar bone and gingiva were harvested for biopsy. Histological examination revealed bacterial colonies at the bottom of the sulcus. Infiltration of chronic inflammatory cells underneath the non-keratinized sulcular epithelium was noted, with abundant capillaries being filled with red blood cells. Proximal alveolar bone facing the bottom of the gingival sulcus exhibited active bone remodeling and woven bone formation with plump osteocytes in the lacunae. On the other hand, buccal alveolar bone exhibited lamination, indicating slow bone turnover in the lateral region.

High Fiber Diets Slow Bone Turnover in Young Men but Have No Effect on Efficiency of Intestinal Calcium Absorption

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Bone remodeling in the longest living rodent, the naked mole-rat: Interelement variation and the effects of reproduction.

The pattern of bone remodeling of one of the most peculiar mammals in the world, the naked mole-rat (NMR), was assessed. NMRs are known for their long lifespans among rodents and for having low metabolic rates. We assessed long-term in vivo bone labeling of subordinate individuals, as well as the patterns of bone resorption and bone remodeling in a large sample including reproductive and non-reproductive individuals (n=70). Over 268 undecalcified thin cross-sections from the midshaft of humerus, ulna, femur and tibia were analyzed with confocal fluorescence and polarized light microscopy. Fluorochrome analysis revealed low osteogenesis, scarce bone resorption and infrequent formation of secondary osteons (Haversian systems) (i.e., slow bone turnover), thus most likely reflecting the low metabolic rates of this species. Secondary osteons occurred regardless of reproductive status. However, considerable differences in the degree of bone remodeling were found between breeders and non-breeders. Pre-reproductive stages (subordinates) exhibited quite stable skeletal homeostasis and bone structure, although the attainment of sexual maturity and beginning of reproductive cycles in female breeders triggered a series of anabolic and catabolic processes that up-regulate bone turnover, most likely associated with the increased metabolic rates of reproduction. Furthermore, bone remodeling was more frequently found in stylopodial elements compared to zeugopodial elements. Despite the limited bone remodeling observed in NMRs, the variation in the pattern of skeletal homeostasis (interelement variation) reported here represents an important aspect to understand the skeletal dynamics of a small mammal with low metabolic rates. Given the relevance of the remodeling process among mammals, this study also permitted the comparison of such process with the well-documented histomorphology of extinct therapsids (i.e., mammalian precursors), thus evidencing that bone remodeling and its endocortical compartmentalization represent ancestral features among the lineage that gave rise to mammals. It is concluded that other factors associated with development (and not uniquely related to biomechanical loading) can also have an important role in the development of bone remodeling.

Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice.

Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and vitamin K2 is more efficient than the control diet to maintain bone quality.

Biodistribution of Fracture-Targeted GSK3β Inhibitor-Loaded Micelles for Improved Fracture Healing.

Bone fractures constitute a major cause of morbidity and mortality especially in the elderly. Complications associated with osteoporosis drugs and the age of the patient slow bone turnover and render such fractures difficult to heal. Increasing the speed of fracture repair by administration of a fracture-targeted bone anabolic agent could find considerable application. Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. Unfortunately, they can also cause significant toxicity when administered systemically and are furthermore difficult to deliver due to their strong hydrophobicity. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to assemble into micelles, extending its circulation time while maintaining its fracture-targeting abilities. For measurement of pharmacokinetics, an 125I was introduced at the location of the bromine in the GSK3β inhibitor to minimize any structural differences. Biodistribution studies demonstrate a greater than 4-fold increase in fracture accumulation over healthy bone.

Peripheral Bone Mineral Density and Bone Turnover in Postmenopausal Women with Type 2 Diabetes

Objective: Several studies have suggested that diabetes affects Bone Mineral Density (BMD). In this study, we investigated the effect of type 2 diabetes mellitus (T2DM) on BMD and the rate of bone turnover in postmenopausal women. Methods: This is a cross-sectional study, in which we measured peripheral bone density and markers of bone turnover in 60 postmenopausal women with T2DM and 48 age, alcohol intake and physical activity - matched control postmenopausal women without diabetes. Results: BMD was significantly greater in subjects with T2DM than controls (0.51 gm/cm2 vs. 0.47 gm/cm2, p<0.01). Women with T2DM also had higher Body Mass Index (BMI) than the control group (mean: 33.7 kg/m2 vs. 26.7 kg/m2, p<0.0001). The difference in BMD between the two groups became non-significant after adjusting for the effect of BMI by multiple regression analysis (p=0.091). Osteocalcin, a marker of bone formation and three markers of bone resorption (cross-linked-N-telopeptides [NTX], C-telopeptides of type 1 collagen [CTX], and Helical peptide) were significantly reduced in T2DM compared with controls. However, the difference in the three bone resorption markers also became insignificant after adjusting for BMI. Conclusion: This study has shown that postmenopausal women with type 2 Diabetes Mellitus apparently have higher BMD and slow bone turnover when compared with matched controls. However, the difference in BMD between the two groups became non-significant after adjusting for the effect of BMI. This study therefore does not provide evidence that T2DM per se affects bone mineral density in postmenopausal women.

Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease

Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit. Children with newly diagnosed IBD can have low bone mineral density and disturbed bone metabolism, but the tissue level characteristics of the bone involvement in pediatric IBD have not been elucidated. In the present study, we evaluated the skeletal status, including static histomorphometry on transiliac bone samples, in 20 patients (age range 8.4 to 17.7 years, 12 boys) with newly diagnosed IBD and compared results to published normative data. Despite normal height (mean Z-score 0.04, SD 1.2), areal bone mineral density at the lumbar spine was moderately low (mean age- and sex-specific Z-score -0.8, SD 1.1). Total body bone mineral content and lean mass were low for age and sex as well (mean Z-scores -1.2, SD 0.9 and -2.0, SD 0.9, respectively). Biochemical bone markers indicated low bone formation and resorption activity. Bone histomorphometry revealed a slightly low cortical width (mean 23%, SD 25%, below the result expected for age) but a normal amount of trabecular bone. The percentage of trabecular bone surface covered by osteoid or osteoclasts was low, suggesting that both bone formation and bone resorption were suppressed. Our results indicate that young patients manifest a mild cortical bone deficit at the iliac crest and slow trabecular bone turnover even at diagnosis, in the setting of IBD.

O3 Residual (ghost) sockets in bisphosphonate use—evidence of poor healing and slow bone turnover

O3 Residual (ghost) sockets in bisphosphonate use—evidence of poor healing and slow bone turnover

Maximizing Effectiveness of Bisphosphonate Therapy for Osteoporosis

While highly prevalent, osteoporosis is greatly underdiagnosed and undertreated in clinical practice. Even when appropriate treatments are prescribed, patient adherence to bisphosphonate therapy is low. As osteoporosis is a silent disease, and therapy is required for many months before benefit is realized, strategies to increase bone mineral density (BMD) and improve medication adherence are important aspects of every patient's care plan. Osteoporotic bone loss occurs without symptoms, and there are often no warning signs before a fracture occurs. Osteoporotic fractures are the most severe consequence of osteoporosis. Bisphosphonates are the most frequently prescribed treatment option for postmenopausal osteoporosis, as they effectively increase BMD, slow bone turnover, and reduce fracture rates. Strategies to improve adherence to osteoporosis therapy include reducing dosing frequency, changing the route of administration, educating the patient about optimum bisphosphonate administration, and sending patient reminders.

Influence gene vdr3 genotypes and alleles on bone turnover in early postmenopausae

Studies on the genetics have focused on the regulation of bone mineral density (BMD) a major predictor of osteoporotic fracture risk. Evidence for a genetic contribution to BMD regulation comes primarily from twin studies thats hawed that between 5070 % of variance in BMD is caused by genetic factors. A great deal of research has been done on gene candidate VDR.3 on 176 postmenopausal women (108 natural menopause and 69 surgical menopause). Polymorphisms of vitamin D receptor have been associated in our group with the speed of bone turnover, registries by DEXA with interval 12 months and DDR test. The every second patient with genotype tt has chance to accompany group with osteoporosis in postmenopausae. In group of women with highs speed of bone turnover frequency t allel in 3 time more than in group with slow bone turnover.

Protocol for assessing bone health in humans by tracing long-lived 41Ca isotope in urine, serum, and saliva samples

2 Slow bone turnover rate and large day-to-day variation in excreted bone biomarkers create a challenge in assessing bone health in humans [1]. The use of the longlived radioisotope 41-calcium (41Ca; t1/2D»10 years), which has a rare natural abundance (41Ca/CaD»10i15), and accelerator mass spectrometry (AMS)1, which is able to detect 41Ca tracer, show great promise in resolving bone health issues [2–4]. However, sample processing for AMS measurements is a barrier to widespread Ca– AMS applications [5]. This communication summarizes an improved protocol for quantifying 41Ca concentrations in biological specimens. Calcium isotope tracers are present in multiple body pools. Saliva sampling is proposed as a noninvasive alternative to blood sampling in a week-long study of two subjects using stable Ca isotopes [6]. Urine is the ultimate noninvasive sample and is known to reXect average plasma levels [4], but high temporal resolution requires direct blood sampling. The previous AMS preparation protocol [4] did not address measurements of either saliva or serum specimens. Our protocol increases sample throughput at a reduced cost and expands routine 41Ca tracer determinations to a wider range of biological specimens including urine, serum, and saliva samples. Urine, fasting blood, and fasting saliva samples were collected at diVerent time points from a healthy post-

A disease of the osteoblast

The human body is made up of hard and soft tissues. The role of the hard tissue, the skeleton, besides being the main reservoir of minerals serving homeostatic mechanisms, is mechanical. Bones offer protection, support, and, most importantly for the purpose of this discussion, they provide anchorage points for striated muscles, which permit posture and movement. We take for granted that bones are hard and will resist the forces normally applied to them. We also accept that, with age, bone will be affected by senescence and will lose mass and resistance, resulting in fractures, decreased mobility, and chronic pain. But nobody expects such a clinical picture in a neonate, which is why many parents who take children with such symptoms to hospital are often suspected of abuse before severe osteogenesis imperfecta is diagnosed. Osteogenesis imperfecta, or brittle bone disease, is a heterogeneous syndrome. Some children have frequent fractures, which compromise survival, whereas others will have only a few fractures during childhood. There is no cure. Supportive care based on well defined occupational therapy or physiotherapy, timely corrective surgery of deformities, and control of chronic pain have helped, but they are unable to alter the natural course of the disease. Linkage studies have established an association between the disease and two genes (COL1A1 and COL1A2) that encode polypeptide chains that make up the type I collagen triple helix, the major component of bone matrix. Over 250 mutations have been characterised in both of these genes. However, trying to correlate mutations and severity of phenotype has been difficult, frustrating, and unsuccessful. Patients with identical mutations can have different degrees of disease severity. Additionally, data from laboratories that analyse collagen structure indicate that no collagen mutations can be found in about 25% of severe cases. Other factors are probably, therefore, involved in development of disease. Histological studies, for example, have allowed the characterisation of new forms of osteogenesis imperfecta with specific alterations (disorganised matrix, mineralisation defect, &c), and no detectable collagen mutations. Indeed, the pathophysiology of bone lesions in osteogenesis imperfecta remains unknown. Osteogenesis imperfecta is a disease of the osteoblast. The osteoblast produces an abnormal matrix that does not respond to mechanical loads. In compensation, the osteoblast population increases and osteoclast activity is raised, leading to a high bone turnover rate. Attempts to improve bone mass and structure with calcitonin, cortisone, growth hormone, parathyroid hormone, thyroxin, vitamins A, C, and D, and minerals (aluminium, calcium, fluoride, magnesium phosphate, and strontium) have not been encouraging. Furthermore, growth hormone increases bone mass in some patients, but the effects seem secondary to a promotion of growth rather than a direct effect on mass. Increased rate of bone turnover is compounded by secondary bone loss induced by immobilisation caused by lower limb fractures. In adults, bisphosphonates decrease this bone loss and slow bone turnover. In a group of 30 severely affected patients, bone mineral density and physical activity greatly increased, fracture rate decreased, and chronic pain disappeared, resulting in improved quality of life. Furthermore, several children confined to wheelchairs were able to walk (figure). No adverse effects on growth or bone modelling and repair have been seen. Such treatment can also be used in infants, in whom results are even better. Growth rate seems to be stimulated under therapy, suggesting that bisphosphonates might have a positive effect on bone formation. At the bone level, the main effect of the drug seems to be a thickening of cortical bone, with less of an effect on cancellous bone. There is also a decrease in bone turnover that might have immediate benefit, but whose long-term effects remain to be assessed. Bisphosphonates will probably be the treatment of choice for some time. However, because they are a symptomatic treatment and not a cure, bisphosphonates will eventually be superseded by treatment of underlying defects. Many thought that bone marrow transplantation, aimed at introducing normal stem cells, could result in cure. This approach, however, proved hazardous. Other forms of somatic gene therapy are under investigation. However, because of the complexity and variability of the basic abnormalities, this approach will take time to come to fruition. Elsa at 26 months old She received pamidronate for 2 years and had surgery to correct her leg deformities.

Rates of cancellous bone remodeling and turnover in osteopenia associated with primary biliary cirrhosis

Osteoporosis and fracturing are well-recognized manifestations of primary biliary cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that result in bone loss are poorly understood. We used dynamic histomorphometric techniques to measure tissue level rates of cancellous bone resorption, formation, and turnover in 12 premenopausal women with PBC and in 12 normal premenopausal women. We compared these values with estimates of bone resorption and formation obtained concurrently in the same subjects by radiocalcium kinetics and biochemical markers. Rates of bone turnover were analyzed as a function of a risk score that reflects the severity of hepatic disease and cholestasis (Mayo proportional-hazards model). Positive correlations were observed between tissue level and whole skeletal estimates of bone remodeling. At the remodeling site (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by PBC, but wall thickness was decreased. At the level of bone tissues, mean bone turnover was increased in PBC patients but varied widely and increased as hepatic disease and cholestasis worsened. We conclude that PBC causes a reduction in the volume of bone formed at the remodeling site and that the overall level of bone remodeling and turnover in PBC is strongly influenced by the severity of hepatic disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be decreased by therapeutic agents that slow bone turnover, and that further bone loss may be halted by liver transplantation.

Effects of a diphosphonate (disodium etidronate; EHDP) on phosphate metabolism in Paget’s disease of bone, primary hyperparathyroidism and type I hypophosphataemic rickets

Disodium etidronate (disodium ethane-l-hydroxy-1,1-diphosphonate; EHDP) is structurally related to inorganic pyrophosphate but contains a P-C-P bond and is therefore resistant to hydrolytic enzymes. Because of its ability to slow bone turnover in experimental animals (9), it is under investigation in man as a treatment for Paget’s disease of bone (1).