The role of muscle loading on bone (Re)modeling at the developing enthesis.

Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (re)modeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral shoulders injected with saline and a separate group of normal mice. It was hypothesized that muscle unloading would suppress bone formation and enhance bone resorption at the enthesis, and that the unloading-induced bony defects could be rescued by suppressing osteoclast activity. In order to modulate osteoclast activity, mice were injected with the bisphosphonate alendronate. Bone formation was measured at the tendon enthesis using alizarin and calcein fluorescent labeling of bone surfaces followed by quantitative histomorphometry of histologic sections. Bone volume and architecture was measured using micro computed tomography. Osteoclast surface was determined via quantitative histomorphometry of tartrate resistant acid phosphatase stained histologic sections. Muscle unloading resulted in delayed initiation of endochondral ossification at the enthesis, but did not impair bone formation rate. Unloading led to severe defects in bone volume and trabecular bone architecture. These defects were partially rescued by suppression of osteoclast activity through alendronate treatment, and the effect of alendronate was dose dependent. Similarly, bone formation rate was increased with increasing alendronate dose across loading groups. The bony defects caused by unloading were therefore likely due to maintained high osteoclast activity, which normally decreases from neonatal through mature timepoints. These results have important implications for the treatment of muscle unloading conditions such as neonatal brachial plexus palsy, which results in shoulder paralysis at birth and subsequent defects in the rotator cuff enthesis and humeral head.

Effect of bone morphogenetic protein 2 on tendon-to-bone healing in a canine flexor tendon model.

Tendon-to-bone healing is typically poor, with a high rate of repair-site rupture. Bone loss after tendon-to-bone repair may contribute to poor outcomes. Therefore, we hypothesized that the local application of the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) would promote bone formation, leading to improved repair-site mechanical properties. Intrasynovial canine flexor tendons were injured in Zone 1 and repaired into bone tunnels in the distal phalanx. BMP-2 was delivered to the repair site using either a calcium phosphate matrix (CPM) or a collagen sponge (COL) carrier. Each animal also received carrier alone in an adjacent repair to serve as an internal control. Repairs were evaluated at 21 days using biomechanical, radiographic, and histologic assays. Although an increase in osteoid formation was noted histologically, no significant increases in bone mineral density occurred. When excluding functional failures (i.e., ruptured and gapped repairs), mechanical properties were not different when comparing BMP-2/CPM groups with carrier controls. A significantly higher percentage of BMP-2 treated specimens had a maximum force <20 N compared to carrier controls. While tendon-to-bone healing can be enhanced by addressing the bone loss that typically occurs after surgical repair, the delivery of BMP-2 using the concentrations and methods of the current study did not improve mechanical properties over carrier alone. The anticipated anabolic effect of BMP-2 was insufficient in the short time frame of this study to counter the post-repair loss of bone.

Intrasynovial flexor tendon repair: a biomechanical study of variations in suture application in human cadavera.

To improve the functional outcomes of intrasynovial tendon suture, prior experiments evaluated individual technical modifications used in the repair process. Few studies, however, have assessed the combinatorial effects of those suture modifications in an integrated biomechanical manner, including a sample size sufficient to make definitive observations on repair technique. Two hundred fifty-six flexor tendon repairs were performed in human cadavera, and biomechanical properties were determined. The effects of five factors for flexor tendon repair were tested: core suture caliber (4-0 or 3-0), number of sutures crossing the repair site (four- or eight-strand), core suture purchase (0.75 or 1.2 cm), peripheral suture caliber (6-0 or 5-0), and peripheral suture purchase (superficial or 2 mm). Significant factors affecting the properties of the repair were the number of core suture strands and the peripheral suture purchase. The least significant factors were core suture purchase and peripheral suture caliber. The choice of core suture caliber affected the properties of repair marginally. Based on these results, we recommend that surgeons continue to focus on multi-strand repair methods, as the properties of eight-strand repairs were far better than those of four-strand repairs. To resist gap formation and enhance repair strength, a peripheral suture with 2 mm purchase is also recommended. Finally, since core suture caliber affected some biomechanical properties, including the failure mode, a 3-0 suture could be considered, provided that future in vivo studies can confirm that gliding properties are not adversely influenced.