Loading and skeletal development and maintenance

P Bergmann, J J Body, S Boonen, Y Boutsen, J P Devogelaer, S Goemaere, J Kaufman, J Y Reginster, S Rozenberg, P Bergmann, J J Body, S Boonen, Y Boutsen, J P Devogelaer, S Goemaere, J Kaufman, J Y Reginster, S Rozenberg

Abstract

Mechanical loading is a major regulator of bone mass and geometry. The osteocytes network is considered the main sensor of loads, through the shear stress generated by strain induced fluid flow in the lacuno-canalicular system. Intracellular transduction implies several kinases and phosphorylation of the estrogen receptor. Several extra-cellular mediators, among which NO and prostaglandins are transducing the signal to the effector cells. Disuse results in osteocytes apoptosis and rapid imbalanced bone resorption, leading to severe osteoporosis. Exercising during growth increases peak bone mass, and could be beneficial with regards to osteoporosis later in life, but the gain could be lost if training is abandoned. Exercise programs in adults and seniors have barely significant effects on bone mass and geometry at least at short term. There are few data on a possible additive effect of exercise and drugs in osteoporosis treatment, but disuse could decrease drugs action. Exercise programs proposed for bone health are tedious and compliance is usually low. The most practical advice for patients is to walk a minimum of 30 to 60 minutes per day. Other exercises like swimming or cycling have less effect on bone, but could reduce fracture risk indirectly by maintaining muscle mass and force.

Figures

Figure 1
Figure 1
Mechanotransduction in bone. OC: osteocyte; OB: osteoblast; OCL: osteoclast; Pre-OB: preosteoblast; Pre-OCL: preosteoclast; PG's: prostaglandin (E2 and I); RANK-L: receptor activating NFκB-Ligand; OPG: osteoprotegerin; IGF: insulin-like growth factor; TGF: transforming growth factor; Scl: sclerostin; PTHrP: parathyroid hormone related peptide. Osteocytes sense the fluid flow induced by loading in the lacunocanalicular system; this signal modulates the secretion in the bone microenvironment of factors which can increase bone remodeling while stimulating osteoblast differentiation and activity (green arrows) and decreasing osteoclast activity (red arrow), resulting locally in a positive bone balance.
Figure 2
Figure 2
Disuse produces a dramatic bone loss in paraplegic patients, more so in trabecular rich bone areas (pelvis) than in areas containing relatively more cortical bone (femurs and tibias) (redrawn from Wilmet et al. [97]).
Figure 3
Figure 3
BMC increases more in children submitted for 7 months to a program of impact exercise (jumps) than in their control peers who had nonimpact activities. Age at onset was 8 years. Seven years after the end of the program, a small benefit of the impact activities was still detectable. Reproduced from Gunter et al. [142], with kind permission of Wiley.
Figure 4
Figure 4
Evolution of hip BMD in a group of osteoporotic postmenopausal women randomized into a fast walking program (filled circles, n = 48), compared to 44 controls (open circles). The slight difference at one year was significant (P = .04). Reproduced from Bergström et al. Osteoporos Int 2008; 19: 177-83 [169], with kind permission of Springer.

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