RESUMO
CONTEXT: Marrow adipose tissue (MAT) has a peripheral to central distribution in adults, higher in peripheral bones. Similarly, the spine has a caudal to cephalad MAT distribution, higher in lumbar vertebras. Diet and the level of physical activities are known modulators of MAT with significant impact on bone; however, whether these can modulate the MAT gradient is unknown. OBJECTIVE: To measure the effect of high protein diet and bed rest interventions on the lumbar MAT gradient. DESIGN PARTICIPANTS INTERVENTION: In a prospective randomized crossover trial, 10 healthy men participated in 2 consecutive campaigns of 21days head-down-tilt-bed-rest (HDTBR). They received either whey protein and potassium bicarbonate-supplemented or control diet separated by a 4-month washout period. MAIN OUTCOME MEASURES: Ten serial MRI measures of lumbar vertebral fat fraction (VFF) were performed at baseline, 10days and 20days of HDTBR and 3 and 28days after HDTBR of each bed rest campaign. RESULTS: The mean L5-L1 VFF difference of 4.2 ± 1.2 percentage point higher at L5 (p = 0.008) constituted a caudal to cephalad lumbar MAT gradient. High protein diet did not alter the lumbar VFF differences during both HDTBR campaigns (all time points p > 0.05). Similarly, 2 campaigns of 21days of HDTBR did not change the lumbar VFF differences (all time points p > 0.05). CONCLUSIONS: This pilot study established that the lumbar vertebral MAT gradient was not altered by a high protein nor by 2 × 21days bed rest interventions. These findings demonstrated that this lack of mechanical stimulus was not an important modulator of the lumbar MAT gradient. The highly preserved MAT gradient needs to be measured in more situations of health and disease and may potentially serve to detect pathological situations.
RESUMO
Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 µM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T1ρ and T2 ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T1ρ and T2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016.