A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse

Bone remodelling around a stem is an unavoidable long-term physiological process highly related to implant design. For some predisposed patients, it can lead to periprosthetic bone loss secondary to severe stress-shielding, which is thought to be detrimental by contributing to late loosening, late periprosthetic fracture, and thus rendering revision surgery more complicated. However, these concerns remain theoretical, since late loosening has yet to be documented among bone ingrowth cementless stems demonstrating periprosthetic bone loss associated with stress-shielding. Because none of the stems replicate the physiological load pattern on the proximal femur, each stem design is associated with a specific load pattern leading to specific adaptive periprosthetic bone remodelling. In their daily practice, orthopaedic surgeons need to differentiate physiological long-term bone remodelling patterns from pathological conditions such as loosening, sepsis or osteolysis. To aid in that process, we decided to clarify the behaviour of the five most used femoral stems. In order to provide translational knowledge, we decided to gather the designers’ and experts’ knowledge and experience related to the design rationale and the long-term bone remodelling of the following femoral stems we deemed ‘legendary’ and still commonly used: Corail (Depuy); Taperloc (Biomet); AML (Depuy); Alloclassic (Zimmer); and CLS-Spotorno (Zimmer).Cite this article: EFORT Open Rev 2018;3:45-57. DOI: 10.1302/2058-5241.3.170024

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Local and Systemic Responses in Matrix Metalloproteinase 8-Deficient Mice during Porphyromonas gingivalis-Induced Periodontitis

Infection and Immunity ◽

10.1128/iai.00873-08 ◽

2008 ◽

Vol 77 (2) ◽

pp. 850-859 ◽

Cited By ~ 107

Author(s):

Heidi Kuula ◽

Tuula Salo ◽

Emma Pirilä ◽

Anita M. Tuomainen ◽

Matti Jauhiainen ◽

...

Keyword(s):

Bone Loss ◽

Matrix Metalloproteinase ◽

Porphyromonas Gingivalis ◽

Alveolar Bone ◽

Inflammatory Responses ◽

Density Lipoprotein ◽

Alveolar Bone Loss ◽

Type I ◽

Site Specific ◽

Vldl Particle

ABSTRACT Periodontitis is a bacterium-induced chronic inflammation that destroys tissues that attach teeth to jaw bone. Pathologically excessive matrix metalloproteinase 8 (MMP-8) is among the key players in periodontal destruction by initiating type I collagen degradation. We studied MMP-8 in Porphyromonas gingivalis-induced periodontitis by using MMP-8-deficient (MMP8 −/− ) and wild-type (WT) mice. Alveolar bone loss, inflammatory mediator expression, serum immunoglobulin, and lipoprotein responses were investigated to clarify the role of MMP-8 in periodontitis and systemic inflammatory responses. P. gingivalis infection induced accelerated site-specific alveolar bone loss in both MMP8 −/− and WT mice relative to uninfected mice. The most extensive bone degradation took place in the P. gingivalis-infected MMP8 −/− group. Surprisingly, MMP-8 significantly attenuated (P < 0.05) P. gingivalis-induced site-specific alveolar bone loss. Increased alveolar bone loss in P. gingivalis-infected MMP8 −/− and WT mice was associated with increase in gingival neutrophil elastase production. Serum lipoprotein analysis demonstrated changes in the distribution of high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) particles; unlike the WT mice, the MMP8 −/− mice underwent a shift toward a smaller HDL/VLDL particle sizes. P. gingivalis infection increased the HDL/VLDL particle size in the MMP8 −/− mice, which is an indicator of lipoprotein responses during systemic inflammation. Serum total lipopolysaccharide activity and the immunoglobulin G-class antibody level in response to P. gingivalis were significantly elevated in both infected mice groups. Thus, MMP-8 appears to act in a protective manner inhibiting the development of bacterium-induced periodontal tissue destruction, possibly through the processing anti-inflammatory cytokines and chemokines. Bacterium-induced periodontitis, especially in MMP8 −/− mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.

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Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip

Journal of Internal Medicine ◽

10.1111/j.1365-2796.2006.01640.x ◽

2006 ◽

Vol 259 (6) ◽

pp. 598-605 ◽

Cited By ~ 126

Author(s):

Y. Z. BAGGER ◽

L. B. TANKO ◽

P. ALEXANDERSEN ◽

G. QIN ◽

C. CHRISTIANSEN ◽

...

Keyword(s):

Bone Loss ◽

Fracture Risk ◽

Site Specific ◽

A Site

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Zoledronic Acid Increases Bone Mineral Density in Patients with Thalassemia Intermedia-Induced Osteoporosis Regardless of the Incessant Bone Marrow Expansion.

Blood ◽

10.1182/blood.v110.11.3813.3813 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3813-3813

Author(s):

Ersi Voskaridou ◽

Dimitrios Christoulas ◽

Lito Antoniadou ◽

Panagiotis Tsaftaridis ◽

Eleni Plata ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Marrow ◽

Placebo Group ◽

Zoledronic Acid ◽

Bone Loss ◽

Bone Pain ◽

Bone Remodelling ◽

Erythropoietic Activity ◽

Mineral Density ◽

Marrow Expansion

Abstract Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Its pathogenesis is multifactorial, and includes mainly bone marrow expansion, endocrine dysfunction and iron overload. Patients with thalassaemia intermedia (TI) seem to have a more expanded bone marrow with pressure on cortical bone, which causes pain and bone loss in several cases. The measurement of soluble transferrin receptor (sTfR) and erythropoietin (Epo) in the serum is considered as accurate marker of erythropoietic activity in thalassemia. Bisphosphonates are potent inhibitors of osteoclast activity and have been used for the management of thalassemia-induced osteoporosis. The aim of this study was to evaluate the effect of zoledronic acid, the most potent aminobisphosphonate, on bone mineral density (BMD) of patients with TI and explore possible correlations with bone marrow expansion and erythropoietic activity. Thirty-five patients with TI and osteopenia or osteoporosis (13M/22F, median age 45 years) were evaluated. Twenty-three were randomized to receive zoledronic acid, 4 mg, IV, every 3 months (n=12) or every 6 months (n=11) for one year, while 12 patients received placebo every 3 months. There was no difference in terms of the presence of gonadal dysfunction between the three studied groups. BMD of the lumbar spine (L), femoral neck and forearm was determined in all patients, using DEXA, before and 12 months after treatment. Bone marrow expansion was assessed by the measurement of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA), before and 12 months post zoledronic acid or placebo administration. In all patients markers of bone remodelling, such as C-telopeptide of collagen type-I (CTX) and bone specific alkaline phosphatase (bALP) were also measured by ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark, and Quidel, San Diego, CA, USA, respectively). Patients were asked to quantify their degree of bone pain on Huskisson’s visual analogue scale and the McGill-Melzack scoring system before and 12 months post-therapy. All patients had increased values of sTfR, Epo, CTX, and bALP compared with 40 controls of similar age and gender (p<0.001). Patients who received zoledronic acid showed a significant increase in their L-BMD (p=0.01), which was accompanied by a dramatic reduction in CTX and bALP values ((p<0.001). There was no difference in terms of L-BMD changes between zoledronic acid groups. Placebo group showed an aggravation of L-BMD (p=0.041) and markers of bone remodelling at 12 months. No other changes were observed in the BMD of other sites. Zoledronic acid reduced bone pain, which remained stable in placebo group during the study period. There was only weak correlation between baseline sTfR levels and L-BMD, while there was no correlation between Epo or hemolytic parameters (indirect bilirubin, reticulocytes counts, and LDH) with BMD of all studied sites. Serum sTfR and Epo values showed a significant elevation after 12 months of therapy in all studied groups (p<0.01, p<0.02, and p<0.01, respectively); this elevation was irrespective of the L-BMD changes. This study suggests that the increase of BMD produced by zoledronic acid in TI is irrespective of the continuous increase of bone marrow expansion, which is considered a major cause of bone loss in this hemoglobinopathy.

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P27. Variations in gastrointestinal calcium absorption: responsible for heterogeneity of bone remodelling and rates of bone loss in femal type 1 osteoporosis

Bone ◽

10.1016/8756-3282(94)90950-4 ◽

1994 ◽

Vol 15 (1) ◽

pp. 123

Author(s):

M Tellez ◽

EB Mawer ◽

A Diaz ◽

M Arlot ◽

R Hesp ◽

...

Keyword(s):

Bone Loss ◽

Calcium Absorption ◽

Bone Remodelling

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Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss

Journal of Endocrinology ◽

10.1530/joe-18-0214 ◽

2018 ◽

Vol 239 (2) ◽

pp. 215-227 ◽

Cited By ~ 7

Author(s):

Guillaume Mabilleau ◽

Benoit Gobron ◽

Aleksandra Mieczkowska ◽

Rodolphe Perrot ◽

Daniel Chappard

Keyword(s):

Bone Loss ◽

Bone Strength ◽

Bone Remodelling ◽

Bone Matrix ◽

The Body ◽

Whole Body ◽

Matrix Composition ◽

Carbonate Substitution ◽

Alendronate Treatment ◽

Gip Receptor

Glucose-dependent insulinotropic polypeptide (GIP) has been recognized in the last decade as an important contributor of bone remodelling and is necessary for optimal bone quality. However, GIP receptors are expressed in several tissues in the body and little is known about the direct vs indirect effects of GIP on bone remodelling and quality. The aims of the present study were to validate two new GIP analogues, called [d-Ala2]-GIP-Tag and [d-Ala2]-GIP1–30, which specifically target either bone or whole-body GIP receptors, respectively; and to ascertain the beneficial effects of GIP therapy on bone in a mouse model of ovariectomy-induced bone loss. Both GIP analogues exhibited similar binding capacities at the GIP receptor and intracellular responses as full-length GIP1–42. Furthermore, only [d-Ala2]-GIP-Tag, but not [d-Ala2]-GIP1–30, was undoubtedly found exclusively in the bone matrix and released at acidic pH. In ovariectomized animals, [d-Ala2]-GIP1–30 but not [d-Ala2]-GIP-Tag ameliorated bone stiffness at the same magnitude than alendronate treatment. Only [d-Ala2]-GIP1–30 treatment led to significant ameliorations in cortical microarchitecture. Although alendronate treatment increased the hardness of the bone matrix and the type B carbonate substitution in the hydroxyapatite crystals, none of the GIP analogues modified bone matrix composition. Interestingly, in ovariectomy-induced bone loss, [d-Ala2]-GIP-Tag failed to alter bone strength, microarchitecture and bone matrix composition. Overall, this study shows that the use of a GIP analogue that target whole-body GIP receptors might be useful to improve bone strength in ovariectomized animals.

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