The contribution of cortical and trabecular tissues to bone strength: insights from denosumab studies

Iolascon, Giovanni; Napolano, Rosa; Gioia, Margherita; Moretti, Antimo; Riccio, Ilaria; Gimigliano, Francesca

doi:10.11138/ccmbm/2013.10.1.047

Cited by 25 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, a low Mg diet did not affect extrinsic biomechanical properties. Cortical components have a prominent role in bone strength [ 27 ], which may explain why a low Mg diet did not affect extrinsic biomechanical properties despite a decrease in trabecular BMD and intrinsic biomechanical properties. In contrast, some approximations were made in calculating bone geometry for mechanical properties, or there could be a measurement sensitivity issue with the whole bone mechanical testing, which may also explain this inconsistency.…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary gelatin hydrolysates on bone mineral density in magnesium-deficient rats

Noma

Takasugi

Shioyama

et al. 2017

BMC Musculoskelet Disord

View full text Add to dashboard Cite

BackgroundThe major types of commercially available gelatin hydrolysates are prepared from mammals or fish. Dietary gelatin hydrolysates from mammals were reported to improve bone mineral density (BMD) in some animal models. In contrast, there is limited study showing the effects of dietary gelatin hydrolysates from fish on BMD. The quantity and structure of peptides in the plasma after oral administration of gelatin hydrolysates depend on the gelatin source, which suggests that the biological activity of gelatin hydrolysates depend on the gelatin source. This study examined the effects of fish-derived gelatin hydrolysate (FGH) or porcine-derived gelatin hydrolysate (PGH) intake on BMD and intrinsic biomechanical properties in magnesium (Mg)-deficient rats as a model showing the decrease in both BMD and intrinsic biomechanical properties.MethodsFour-week-old male Wistar rats were assigned into four groups: a normal group was fed a normal diet (48 mg Mg/100 g diet), a Mg-deficient (MgD) group was fed a MgD diet (7 mg Mg/100 g diet), a FGH group was fed a MgD + FGH diet (5% FGH), and a PGH group was fed a MgD + PGH diet (5% PGH) for 8 weeks. At the end of the study, BMD and intrinsic biomechanical properties of the femur were measured.ResultsThe MgD group showed significantly lower Young’s modulus, an intrinsic biomechanical property, and trabecular BMD of the femur than the normal group; however, the MgD diet did not affect cortical BMD and cortical thickness. Both the FGH and the PGH groups showed significantly higher cortical thickness and ultimate displacement of the femur than the normal group, but neither type of gelatin hydrolysate affected Young’s modulus. Furthermore, the FGH group, but not the PGH group, showed significantly higher trabecular BMD than the MgD group.ConclusionsThis study indicates that FGH and PGH increase cortical thickness but only FGH prevents the decrease in trabecular BMD seen in Mg-deficient rats, while neither type of gelatin hydrolysate affect intrinsic biomechanical properties.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of dietary gelatin hydrolysates on bone mineral density in magnesium-deficient rats

Noma

Takasugi

Shioyama

et al. 2017

BMC Musculoskelet Disord

View full text Add to dashboard Cite

show abstract

“…Because BMD is considered only a surrogate measure of bone strength[58], micro-architecture determinants are necessary to evaluate the true impact of a treatment on trabecular bone quality because trabecular bone is more readily lost in the OVX rodent model[59]. Preservation of the trabecular micro-architecture contributes to bone strength and may reduce fracture risk independently of BMD and BMC[60, 61]. We found that CGA27 and CGA45 significantly improved all parameters of trabecular micro-architecture in the femurs of OVX rats.…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

et al. 2016

View full text Add to dashboard Cite

Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast differentiation by decreasing Shp2, p-Akt, and cyclin D1. This study found that CGA improved the BMD and trabecular micro-architecture for the OVX-induced osteoporosis. Therefore, CGA might be an effective alternative treatment for postmenopausal osteoporosis. CGA promoted proliferation of osteoblast precursors and osteoblastic differentiation of BMSCs via the Shp2/PI3K/Akt/cyclin D1 pathway.

show abstract

“…In one report, denosumab therapy resulted in a significant, early, and sustained increase in bone mineral density (BMD) and enhanced bone strength in the improvement of both cortical and trabecular bones [ 4 ]. Another review described that denosumab treatment for 6 years maintained a low fracture incidence, reduced bone turnover, and an increase in BMD [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study

et al. 2015

View full text Add to dashboard Cite

BackgroundDenosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan.MethodsHere, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group.ResultsThe bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group.ConclusionsOur results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group.Trial registrationCurrent Controlled Trials NCT02156960. Registered 31 May 2014.

show abstract

The contribution of cortical and trabecular tissues to bone strength: insights from denosumab studies

Cited by 25 publications

References 35 publications

Effects of dietary gelatin hydrolysates on bone mineral density in magnesium-deficient rats

Effects of dietary gelatin hydrolysates on bone mineral density in magnesium-deficient rats

Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study

Contact Info

Product

Resources

About