Osteoarthritis like Alteration of Cartilage and Subchondral Bone Induced by Protein Malnutrition is treated by Nutritional Essential Amino Acids Supplements
C. Lavet Osteoarthritis and Cartilage VOLUME 25, SUPPLEMENT 1, S293, APRIL 01, 2017
Purpose: Osteoarthritis onset and its initial progression is characterized by cartilage matrix deterioration as well as subchondral/cartilage crosstalk alterations. Elderly patients frequently suffer from protein malnutrition leading to major alteration of the somatotropic axis including lower systemic and local IGF-I production known as major anabolic agent for cartilage and bone homeostasis. We postulate that protein malnutrition could affect both cartilage and subchondral bone and may contribute to osteoarthritis development. Additionally we evaluated whether essential amino acids supplements, could restore the somatotropic axis and reverse these potential deleterious effects.
Methods: To address this questions, mature Sprague Dawley rats (6 months old) were pair fed a chow diet (NP, 15% casein, 1 group) or an isocaloric low protein diet (LP, 2.5% casein, 2 groups) for a period of 12 weeks. Following this period, one of the two groups submitted to LP was treated with essential amino acids supplementation (LP+EAA, 2.5%+5% casein). All animals were euthanized and femurs were collected 24 weeks after initiation of the protocol. Phase-contrast micro-computed tomography by using contrast agent allowed determination of trabecular and cortical subchondral bone (SB) morphometric parameters as well as hyaline and calcified cartilage thickness, and proteoglycan content estimation of both condyle. Indentation with Bioindenter equipment (Piuma, Optics 11, Nederland) allowed determination of cartilage material level properties (Young's modulus, indentation force) in three indentation zones of each condyle chosen according to their joint mechanical loading pattern related to rat ambulation.
Results: As expected, systemic IGF-I was decreased after 12 weeks of LP diet (−45%, p<.001) and was associated to lower SB trabecular mass and mineral density (respectively −30% and −3%, p<.001). Despite no morphologic changes of the cartilage of the medial condyle, hyaline cartilage biomechanical properties were impaired. In each investigated zone, and independently of the joint mechanical loading pattern related to rat ambulation, elastic modulus and indentation force necessary to reach a depth of 25 μm were decreased in a respective range of −20 to −45 % (p<.001) and −10 to −30 % (p<.001). Proteoglycan content estimation by micro-computed tomography of both condyle was not altered by LP diet. EAA supplementation restored IGF-I systemic level from 4 weeks of treatment. EEA supplements fully normalized both alteration of SB bone and cartilage quality without alteration of cartilage proteoglycan content.
Conclusions: We suggest that alteration of the somatotropic axis induced by protein malnutrition alters cartilage quality and could predispose to osteoarthritis. The underlying mechanism is still unknown; we did not find any major alteration of cartilage proteoglycan content related to LP diet using phase-contrast micro-computed tomography thus additional histologic study is warranted to demonstrate minor alteration or collagen alteration. Furthermore EAA supplement reverses these alterations. Since protein malnutrition is frequent in elderly this mechanism could be relevant in human as well as a nutritional intervention with essential amino acids supplements.