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After chronic 3-G centrifugation of rats, their bone-to-ligament junctions exhibited 95 +/- 12% of the control junctions' force-sustaining capacity (F). F was actually 29 +/- 5% greater for centrifuged rats than for control rats of comparable size, as experimental animals grew to smaller body mass. This suggests that gravity determines part of F's magnitude. These junctions are, therefore, hypothesized to be weaker after development in a weightless environment. The effect was less measurable for mice. F was measured in situ as load needed to separate the knee's medial collateral ligament from the tibia of 34 male rats (Sprague-Dawley, 27-320 d of age, exposed 4-65 d), 30 control rats, 22 male mice (Swiss Webster, 35-166 d, exposed 9-56 d), and 15 control mice.

The clinical practices of the future depend upon the experimental findings of today. Because of the uniqueness of connective tissue, animal experimentation will be essential for advances in this field. During the last decade, the improvements in technology and the increased interest of basic scientists and research clinicians on the effects of physical activity has markedly enhanced the amount of information available to practicing physicians. Studies spanning the appearances of structure to the changes in the crosslinks of collagen, clearly demonstrate that limb immobilization (inactivity) is deleterious to all structures involved whether evaluated anatomically, physiologically, or biomechanically. Furthermore, when surgical repair is included, there are stages when the deleterious processes become accelerated with or without immobilization. Hence, clinical immobilization must be utilized in a prudent and careful manner. There is sufficient experimental evidence for clinicians to utilize motion and mechanical stimuli as a means to improve the structure and function of tendons, ligaments, and joints. However, the unresolved issues are the mode, time of initiation, or the intensity of application. Even when used with repair, recovery of normal structures and function is protracted. The primary or secondary mechanisms associated with these effects of physical activity are unknown and virtually uninvestigated at the present time.

A double-blind study was conducted to assess the influence of a sclerosing solution on rabbit medial collateral ligaments (MCL) in situ. It was shown that repeated injections of 5% sodium morrhuate into the MCL and its bony attachments significantly increased its bone-ligament-bone junction strength, ligament mass and thickness when compared to saline-injected controls. Morphometric analysis of electron micrographs showed a highly significant corresponding increase of the collagen fibril diameters in the experimental ligament compared against the control MCL. These composite findings suggested that the sclerosing solution had a significant influence on dense connective tissue at the insertion sites. The mechanisms for these changes are uncertain and are the basis for future investigations.

The bone-ligament junction strength of femur-medial collateral ligament-tibia complexes in rats was measured in situ at various ages during a two-year period. Male rats had a higher junction strength than female rats, a difference that became apparent when the animals were sixty days old and in male but not female animals subsequently paralleled the changes in body weight. However, on a bodyweight basis, the junctions were stronger in female than in male rats and this sex difference was evident at fifteen days old and persisted thereafter. Regression analysis between body weight and junction strength indicated that female rats had a significantly higher slope than males, which suggested that the sex differences were due to a hormonal factor or factors. Other measurements showed that elastic stiffness, failure energy, and collagen concentration in the ligament increased, whereas the water content of the ligament decreased with age. Most of these changes could be attriubted to the aging process and not the sex of the animal. It was concluded, however, that the strength of the insertion sites of ligaments on bones are responsive to the hormonal fluctuations that occur with aging.

Using either a bone-ligament-bone or a muscle-tendon-bone preparation, numerous investigators have demonstrated that the usual site of separation is in the transitional zone between the ligament (or tendon) and bone; hence, the term junction strength or load at separation is used to describe functional changes in these preparations. Junction strength is decreased with inactivity (immobilization) and increased with chronic activity (training) provided that the exercise program is of an endurance nature. Training also increases junction strength in thyroidectomized and hypophysectomized rats. Besides in junction strength, training results in heavier ligaments and higher ligament weight/length ratios. However, water content, collagen concentrations/dry weight or collagen concentration per weight/length unit are not significantly influenced by repeated bouts of exercise. Although immobilization is associated with lower elastic stiffness values (kg/mm), training appears to have little influence on this measure in normal animals. Rats and dogs with surgically repaired ligaments are weaker and the strength results are markedly lower if the leg is immobilized. Exercise training improves the repair strength of ligaments but does not result in normal values twelve weeks after the surgery. Exogenous administration of ICSH or testosterone results in higher repair strength whereas TSH, thyroxine, ACTH and growth hormone decreases this measure. It was concluded that the mechanical stress produced by chronic exercise is an important determination of the strength of repaired ligaments and of the junctions between ligaments (or tendons) and bones.