Farrell, Peter A.

The ability of bone to respond to increased loading as a function of age was tested by use of three-point bending and histomorphometry. The hindlimbs of male Fischer 344 rats of three age groups (young = 4 mo, adult = 12 mo, and old = 22 mo; n = 10 per age group) were progressively overloaded by training the rats to depress a lever high on the side of a cage while wearing a weighted backpack. This squatlike movement required full extension of the hindlimbs. Exercised (Exer) rats performed 50 repetitions three times per week for 9 wk. Pack weight was gradually increased to 65% of body weight. Controls ( n = 10 per age group) performed the same exercise without additional weight. Neither the mechanical properties of the femur nor histomorphometry in the proximal tibia was significantly affected in young or adult rats. However, old Exer rats were found to have significantly smaller medullary areas and a decreased trabecular spacing than their age-matched controls. These results suggest a greater sensitivity to increased loading in aged rats.

Westerlind, Kim C., James D. Fluckey, Scott E. Gordon, William J. Kraemer, Peter A. Farrell, and Russell T. Turner.Effect of resistance exercise training on cortical and cancellous bone in mature male rats. J. Appl. Physiol. 84(2): 459–464, 1998.—The effect of resistance training on tibial cancellous and cortical bone was evaluated in rats by using static histomorphometry and Northern analysis. Five-month-old male Sprague-Dawley rats were randomly assigned to exercise (Ex; n = 8) or control (Con; n = 4) groups. Animals were operantly conditioned to press two levers, facilitating full extension and flexion of the hindlimbs (“squats”), while wearing an unweighted vest. After an 8-wk familiarization period, Ex animals performed 3 sessions/wk for 17–19 sessions with progressively increased amounts of weight applied to the vest. Con rats completed the same exercise protocol without applied resistance. No difference in cross-sectional, medullary, or cortical bone area was observed between Ex and Con rats in the tibial diaphysis. In contrast, the cancellous bone area in the proximal tibial metaphysis was significantly larger in trained rats. Trabecular number, trabecular thickness, and the percentage of cancellous bone covered by osteoid were significantly greater in the Ex animals compared with Con animals. In addition, steady-state mRNA levels for osteocalcin for the Ex group were 456% those expressed in the Con group. The data demonstrate that resistance training increases cancellous bone area in sexually mature male rats and suggest that it does so, in part, by stimulating bone formation.

The effect of aging on long bone mechanical properties and bone formative capacity was characterized in the male Fisher 344 rat. The femurs of rats from three age groups (4 mo., 12 mo. and 28 mo.) were tested in three-point bending to determine their structural properties. The apparent material properties were then calculated by adjusting for bone geometry. Bone formation was assessed by dynamic histomorphometry of both cortical and cancellous bone as well as by Northern blot analysis for the expression of the osteoblast phenotypic proteins osteopontin (OP), osteocalcin (OC), type I collagen (COL) and alkaline phosphatase (AP). Aging resulted in a decline in the apparent material properties that was associated with a compensatory alteration of bone geometry that preserved structural strength and stiffness. Histomorphometric analysis revealed significant age-related decreases in cancellous bone volume, trabecular number and increased trabecular separation suggesting the existence of senile osteopenia in the proximal tibia of the male Fisher 344 rat. A significant decline in bone formation rate (BFR), but not mineral apposition rate, suggests that a reduction in osteoblast number, but not osteoblast activity, contributes to age-related bone loss. The decline in BFR with aging was reflected in a decreased mRNA expression for OP, OC and COL but not AP. Further, the pattern of mRNA expression was consistent with reduced osteoblast differentiation with aging. The present study indicates the age-related decline in material properties of long bones is paralleled by a decrease in osteogenesis.