Bone Metabolism In Humans Research Articles

Bones and Joints: The Effects of Cannabinoids on the Skeleton

The endocannabinoid system uses tissue-specific lipid ligands and G protein‒coupled transmembrane receptors to regulate neurologic, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics (e.g., tetrahydrocannabinol and cannabidiol), the involvement of endocannabinoids in bone growth and remodeling has become clinically relevant. This literature review is based on a search of PubMed and Google Scholar databases as of June 2019 for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions. Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited. In vitro and animal models document that endocannabinoids are involved in bone biology. The relevance of these observations to humans is not clear. The increasing long-term use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.

The Effects of Bovine Colostrum in Bone Metabolism in Humans

The Effects of Bovine Colostrum in Bone Metabolism in Humans

The Detrimental Effects of Kynurenine, a Tryptophan Metabolite, on Human Bone Metabolism.

Studies in aged mice support a role for kynurenine, a tryptophan metabolite, in age-induced bone loss; however, the role of kynurenine in human bone metabolism is not well understood. To assess whether the kynurenine level in bone marrow (BM) aspirates, directly reflecting the bone microenvironment, is associated with osteoporosis-related phenotypes and bone biochemical markers. A case-control study conducted in a clinical unit. BM samples were collected from 72 patients at the time of hip surgery for either fragility hip fracture (HF) (n = 27) or for other causes (n = 45). In these samples, kynurenine was measured by liquid chromatography-tandem mass spectrometry, and the levels of tartrate-resistant acid phosphatase 5b (TRAP5b), bone-specific alkaline phosphatase (BSALP), receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) were measured by immunoassay. Age was positively correlated with BM kynurenine level. After adjustment for confounders, subjects with fragility HF had a 39.7% higher BM kynurenine level than those without, and the OR per SD increment in BM kynurenine level for fragility HF was 3.80. The BM kynurenine level was inversely associated with bone mass at the total femur. Higher kynurenine concentrations were significantly associated with higher TRAP-5b and RANKL levels, but not with BSALP and OPG levels, in BM plasma. These results suggest that increased kynurenine levels during aging may contribute to the bone fragility seen in the elderly through increased bone resorption, with a resultant imbalance in bone remodeling.

CALCITONIN REVISITED IN 2020.

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy.

β-Blockers and bone health.

Bone metabolism is controlled by endocrine, paracrine, and inflammatory signals that continuously operate in health and disease. While these signals are critical for skeletal adaptation during development, longitudinal growth, and repair, disturbances such as sex hormone deficiency or chronic inflammation have unambiguously been linked to bone loss and skeletal fragility across species. In the current issue of the JCI, Khosla et al. evaluated the role of sympathetic outflow and present evidence to support the idea that the sympathetic nervous system regulates bone metabolism in humans, primarily via the β1-adrenergic receptor.

Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.

Evidence from rodent studies indicates that the sympathetic nervous system (SNS) regulates bone metabolism, principally via β2-adrenergic receptors (β2-ARs). Given the conflicting human data, we used multiple approaches to evaluate the role of the SNS in regulating human bone metabolism. Bone biopsies were obtained from 19 young and 19 elderly women for assessment of ADRB1, ADRB2, and ADRB3 mRNA expression. We examined the relationship of β-blocker use to bone microarchitecture by high-resolution peripheral quantitative CT in a population sample of 248 subjects. A total of 155 postmenopausal women were randomized to 1 of 5 treatment groups for 20 weeks: placebo; propranolol, 20 mg b.i.d.; propranolol, 40 mg b.i.d.; atenolol, 50 mg/day; or nebivolol, 5 mg/day. We took advantage of the β1-AR selectivity gradient of these drugs (propranolol [nonselective] << atenolol [relatively β1-AR selective] < nebivolol [highly β1-AR selective]) to define the β-AR selectivity for SNS effects on bone. ADRB1 and ADRB2, but not ADRB3, were expressed in human bone; patients treated clinically with β1-AR-selective blockers had better bone microarchitecture than did nonusers, and relative to placebo, atenolol and nebivolol, but not propranolol, reduced the bone resorption marker serum C-telopeptide of type I collagen (by 19.5% and 20.6%, respectively; P < 0.01) and increased bone mineral density of the ultradistal radius (by 3.6% and 2.9%; P < 0.01 and P < 0.05, respectively). These 3 independent lines of evidence strongly support a role for adrenergic signaling in the regulation of bone metabolism in humans, principally via β1-ARs. ClinicalTrials.gov NCT02467400. This research was supported by the NIH (AG004875 and AR027065) and a Mayo Clinic Clinical and Translational Science Award (CTSA) (UL1 TR002377).

Magnesium calcium silicate bioactive glass doped with copper ions; synthesis and in-vitro bioactivity characterization

Recent studies revealed that metallic ions have therapeutic effects on human bone metabolism and angiogenesis. Thus, in this study, a new magnesium-calcium-silicate glass powder, being doped with copper ions was synthesized through the sol-gel process; the material was termed as 60S7M2Cu. The glass was thermally treated at several temperatures up to 870 °C in order to induce crystallization, which would potentially enhance its mechanical and/or biological properties. Structural and morphological characterization, thermal analysis and in-vitro apatite forming ability evaluation were performed by X-ray diffraction-XRD, Scanning Electron Microscopy-SEM coupled with Energy Dispersion Spectrometry-EDS, Thermogravimetric Analysis, as well as Fourier Transformed Infrared-FTIR Spectrometry. Moreover, the elemental release was recorded by Inductively Coupled Plasma Atomic Emission Spectroscopy ICP-AES. Experimental results showed that a crystalline hydroxyapatite phase was developed after 3 days in the simulated body fluid (SBF) followed, after 15 days, by the growth of a carbon hydroxyapatite layer, in both untreated glass as well as treated glass-ceramics nearly at all temperatures. At lower temperatures, namely 770 and 800 °C, a whitlockite bioactive phase appeared after the immersion in SBF, while a wollastonite crystalline phase emerged when treated at 830 and 870 °C without having a negative effect on its apatite forming ability. Copper ions releasing from the glass and glass-ceramics materials was proved to be slow and stable during the whole period of soaking. In this study copper containing glass and glass-ceramics, which present apatite forming ability and according to literature possess the capability to induce the release of therapeutic ions with osteogenic and angiogenic capacity, were synthesized. Eventually, after further investigations, this glass composition could be applied in bone tissue engineering, where bioactive materials able to induce simultaneously both osteogenesis and angiogenesis constitute a constant demand.

Higher sympathetic activity as a risk factor for skeletal deterioration in pheochromocytoma.

Despite the potential biological importance of sympathetic activity in human bone metabolism, its effects on bone microarchitecture, a key determinant of bone quality, has not been thoroughly studied. In the present study, we investigated the lumbar spine trabecular bone score (TBS) as an indicator of skeletal deterioration in pheochromocytoma. Among 620 consecutive patients with newly diagnosed adrenal incidentaloma, 29 with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 266 with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 2.9% lower lumbar spine TBS than those without pheochromocytoma (P = 0.038). Moreover, urinary normetanephrine level, but not urinary metanephrine level, was inversely correlated with lumbar spine TBS (P = 0.009). Subjects in the highest urinary normetanephrine quartile showed markedly lower lumbar spine TBS than those in the lowest quartile (P = 0.018), in a dose-response manner across increasing urinary normetanephrine quartile categories (P for trend = 0.021). Consistent with the results of previous studies, subjects with pheochromocytoma had significantly lower bone mass at the lumbar spine and higher serum level of C-terminal telopeptide of type I collagen than controls (P = 0.013 and 0.002, respectively). These findings provide clinical evidence that catecholamine excess and the resultant sympathetic overstimulation in pheochromocytoma may contribute to bone fragility, especially in the trabecular bone, through a weak microarchitecture in addition to a lower bone mass and increased bone resorption, and support the possibility of pheochromocytoma as a secondary cause of osteoporosis.

Heterozygous deletion of LRP5 gene in mice alters profile of immune cells and modulates differentiation of osteoblasts.

Skeletal homeostasis is dynamically influenced by the immune system. Low density lipoprotein receptor-related protein-5 (LRP5) is a co-receptor of the Wnt signaling pathway, which modulates bone metabolism in humans and mice. Immune disorders can lead to abnormal bone metabolism. It is unclear whether and how LRP5 alters the balance of the immune system to modulate bone homeostasis. In this study, we used primary osteoblast to detect the differentiation of osteoblasts in vitro, the immune cells of spleen and bone marrow of 6-month old LRP5 heterozygote (HZ) and wild-type (WT) mice were analyzed by Flow cytometry. We found that LRP5+/- could influence the differentiation of osteoblasts by decreasing the mRNA level of Osterix, and increasing the mRNA level of Runx2 and the ratio of receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG). In the LRP5+/- mice, percentages of NK cells, CD3e+ cells, and CD8a+ T cells were increased in both spleen and bone marrow, and percentages of CD106+ cells and CD11c+ cells were increased in spleen while decreased in bone marrow, conversely, CD62L+ cells were decreased in spleen while increased in bone marrow compared to the WT mice. Percentages of CD4+ cells, CD14+ cells, and CD254+ cells were increased in the spleen, and CTLA4+ cells were increased in the bone marrow of the LRP5+/- mice. The mRNA level of Wnt signaling molecules such as β-catenin, and c-myc were decreased and APC was increased in spleen lymphocytes and bone marrow lymphocytes, and the mRNA level of Wnt3a was decreased in spleen lymphocytes while no change in bone marrow lymphocytes was seen with silencing LRP5 by specific small interfering RNA. In conclusion, heterozygous deletion of the LRP5 gene in mice could alter the profile of the immune cells, influence the balance of immune environment, and modulate bone homeostasis, which might present a potential mechanism to explore the Wnt signaling pathway in the modulation of the immune system.

Leptin as an obesity marker in rheumatoid arthritis.

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1β by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1β). Analysis of ROC curves determined the cut-off point of 10.3ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

Effects of Excessive Dietary Phosphorus Intake on Bone Health.

The purpose of this review is to provide an overview of dietary phosphorus, its sources, recommended intakes, and its absorption and metabolism in health and in chronic kidney disease and to discuss recent findings in this area with a focus on the effects of inorganic phosphate additives in bone health. Recent findings show that increasing dietary phosphorus through inorganic phosphate additives has detrimental effects on bone and mineral metabolism in humans and animals. There is new data supporting an educational intervention to limit phosphate additives in patients with chronic kidney disease to control serum phosphate. The average intake of phosphorus in the USA is well above the recommended dietary allowance. Inorganic phosphate additives, which are absorbed at a high rate, account for a substantial and likely underestimated portion of this excessive intake. These additives have negative effects on bone metabolism and present a prime opportunity to lower total phosphorus intake in the USA. Further evidence is needed to confirm whether lowering dietary phosphorus intake would have beneficial effects to improve fracture risk.

Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling

The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies using rodent models. In the current study, we investigated the effects of PGE2 on human bone marrow stromal cell (hBMSC) lineage commitment and determined its mode of action. We demonstrated that PGE2 treatment of hBMSCs significantly altered the expression profile of several genes associated with osteoblast differentiation (RUNX2 and ALP) and maturation (BGLAP and MGP). This was attributed to the activation of specific PGE2 receptors, and was associated with increases in cAMP production and sustained AKT phosphorylation. Pharmacological inhibition of exchange protein directly activated by cAMP (Epac), but not protein kinase A (PKA), recovered the mineralization functions of hBMSC-derived osteoblasts treated with PGE2 and restored AKT phosphorylation, along with the expression levels of RUNX2, ALP, BGLAP and MGP. Our findings therefore provide insights into how PGE2 influences hBMSC-mediated matrix mineralization, and should be taken into account when evaluating the role of PGE2 in human bone metabolism.

Bone Degeneration and Its Recovery in SMP30/GNL-Knockout Mice.

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.

Association of osteoglycin and FAM5C with bone turnover markers, bone mineral density, and vertebral fractures in postmenopausal women with type 2 diabetes mellitus

ObjectiveAccumulating evidence suggests a reciprocal relationship between muscle and bone. Previous in vitro studies showed that the muscle-derived factors, osteoglycin (OGN) and family with sequence similarity 5, member C (FAM5C), regulate osteoblastic differentiation. However, there are no reports investigating the association between circulating OGN and FAM5C and bone metabolism in humans. DesignWe conducted a cross-sectional study and investigated the association of serum OGN and FAM5C levels and muscle mass examined by whole-body dual-energy x-ray absorptiometry with bone mineral density (BMD), bone turnover markers, and the presence of vertebral fractures (VFs) in 156 postmenopausal women with type 2 diabetes mellitus (T2DM). ResultsMultiple regression analysis adjusted for age, duration of T2DM, body mass index, serum creatinine, and log(hemoglobin A1c) showed that log(OGN) was negatively associated with BMD at the femoral neck (β=−0.17, p=0.014). Serum OGN levels were higher in subjects with VFs than in those without VFs [mean±standard deviation (SD): 100.2±84.7 vs. 74.4±31.7pg/mL, p=0.013]. Moreover, logistic regression analysis adjusted for the confounding factors described above showed that the serum OGN level was positively associated with the presence of VFs (odds ratio=1.84, 95% confidence interval=1.03–3.29 per SD increase, p=0.039). In contrast, neither the serum FAM5C level nor muscle mass indices were associated with bone turnover markers and the presence of VFs. ConclusionsThe present study showed for the first time that higher serum OGN levels were associated with decreased BMD and increased risk of vertebral fractures in postmenopausal women with T2DM.

Sclerostin deficiency in humans

Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasias caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis.

Dehydroepiandrosterone(DHEA)and bone metabolism

Dehydroepiandrosterone(DHEA), an adrenal androgen, has attracted much attention as an anti-aging hormone as well as a marker for senescence because of its unique change along with aging. DHEA is reported to have beneficial effects such as anti-diabetes, anti-obesity, and anti-atherosclerosis. It is also shown that DHEA has anti-osteoporosis effects to increase bone mineral density in randomized controlled trials(RCTs). As osteoblasts express aromatase which will convert androgen to estrogen, DHEA may act protectively against osteoporosis through its metabolites. Because there is no report on fracture risk by DHEA administration, further studies are required to clarify DHEA effects on human bone metabolism.

Plasminogen activator inhibitor-1 concentrations and bone mineral density in postmenopausal women with type 2 diabetes mellitus.

BackgroundWomen with type 2 diabetes mellitus (T2DM) have a higher risk of fractures despite increased bone mineral density (BMD). In experimental studies a potential role of plasminogen activator inhibitor-1 (PAI-1) in bone remodeling is suggested but studies in humans are lacking. This is a first study in humans investigating whether circulated levels of PAI-1 in postmenopausal women with T2DM are related to BMD and adiposity.MethodsAnthropometric variables, PAI-1 and insulin levels, serum lipids and bone turnover markers were measured in 127 postmenopausal women with T2DM. A total of 117 female patients were divided according to lumbar spine BMD measurements via dual-energy x-ray absorptiometry in three groups: 47 with osteopenia, 21 with osteoporosis and 49 with normal BMD.ResultsDiabetic patients with normal BMD had significantly higher BMI, greater waist circumference and lower bone turnover markers than diabetics with osteopenia and osteoporosis. PAI-1 was lower in diabetics with osteoporosis and osteopenia compared with diabetics with normal BMD. Multiple regression analysis revealed insulin, triglycerides levels, pyrilinks and beta blocker therapy to be the strongest predictors of PAI-1 levels. PAI-1 levels correlated with both L-BMD and hip BMD, but after adjustment for age and BMI association was no longer significant.ConclusionOur findings suggest that elevated PAI-1 levels are associated with higher BMD in obese diabetic patients but the possible implications of this finding and underlying mechanisms still remain unclear. Obviously, metabolic parameters, may affect both BMD and PAI-levels, and association of PAI-1 and BMD could be indirect. However, as pyrilinks is also independently and significantly negatively correlated to PAI-1 its direct involvement in bone metabolism is also plausible. Further investigations are needed to elucidate the nature of interaction of this matrix modulator in relation to energy and bone metabolism in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-016-0094-x) contains supplementary material, which is available to authorized users.

Effects of dioxin-related compounds on bone mineral density in patients affected by the Yusho incident.

Exposure to dioxin-related compounds results in many adverse health effects. Several studies have examined the effects of dioxin-related compounds on human bone metabolism with inconsistent results. In Japan in 1968, accidental human exposure to rice oil contaminated with dioxin-related compounds led to the development of Yusho oil disease. The aim of this study was to determine whether exposure to dioxin-related compounds was associated with bone mineral density in Yusho patients. In 2010, 262 women and 227 men underwent dual-energy X-ray absorptiometry bone scans as part of the nationwide Yusho health examination. Serum levels of polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls were measured using high-resolution gas chromatography and high-resolution mass spectrometry. When adjusted for prefecture, 1,2,3,4,7,8-HxCDD and 2,3,7,8-TCDF were significantly positively associated with Z-scores in men. No congeners were positively associated with Z-scores in women. After adjustment for prefecture and body mass index, one congener, 1,2,3,4,6,7,8-HpCDD, was negatively associated with Z-scores in women. In contrast, no congeners remained significant in men after adjusting for body mass index. This may suggest that 1,2,3,4,6,7,8-HpCDD has a negative effect on bone mineral density in women; however, the findings should be interpreted carefully, because no increase in the serum level of this congener was observed in patients with Yusho disease.

The effects of acute hyperinsulinemia on bone metabolism

Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m2 per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m2 per min) for 4 h resulted in more pronounced decrease (−32%, P<0.01) whereas shorter insulin exposure (40 mU/m2 per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin.

Bone-remodeling transcript levels are independent of perching in end-of-lay white leghorn chickens.

Osteoporosis is a bone disease that commonly results in a 30% incidence of fracture in hens used to produce eggs for human consumption. One of the causes of osteoporosis is the lack of mechanical strain placed on weight-bearing bones. In conventionally-caged hens, there is inadequate space for chickens to exercise and induce mechanical strain on their bones. One approach is to encourage mechanical stress on bones by the addition of perches to conventional cages. Our study focuses on the molecular mechanism of bone remodeling in end-of-lay hens (71 weeks) with access to perches. We examined bone-specific transcripts that are actively involved during development and remodeling. Using real-time quantitative PCR, we examined seven transcripts (COL2A1 (collagen, type II, alpha 1), RANKL (receptor activator of nuclear factor kappa-B ligand), OPG (osteoprotegerin), PTHLH (PTH-like hormone), PTH1R (PTH/PTHLH type-1 receptor), PTH3R (PTH/PTHLH type-3 receptor), and SOX9 (Sry-related high mobility group box)) in phalange, tibia and femur. Our results indicate that the only significant effect was a difference among bones for COL2A1 (femur > phalange). Therefore, we conclude that access to a perch did not alter transcript expression. Furthermore, because hens have been used as a model for human bone metabolism and osteoporosis, the results indicate that bone remodeling due to mechanical loading in chickens may be a product of different pathways than those involved in the mammalian model.