We have previously shown that the effect of mechanical loading on bone is
partly dependent on connexin43 (Cx43). To determine whether Cx43 is also
involved in the effect of mechanical unloading, we have used botulinum toxin A
(BtxA) to induce reversible muscle paralysis in mice with a conditional deletion
of the Cx43 gene in osteoblasts and osteocytes (cKO). BtxA injection in hind
limb muscles of wild type (WT) mice resulted in significant muscle atrophy and
rapid loss of trabecular bone. Bone loss reached a nadir of about 40% at
3 weeks post-injection, followed by a slow recovery. A similar degree of
trabecular bone loss was observed in cKO mice. By contrast, BtxA injection in WT
mice significantly increased marrow area and endocortical osteoclast number, and
decreased cortical thickness and bone strength. These changes did not occur in
cKO mice, whose marrow area is larger, osteoclast number higher, and cortical
thickness and bone strength lower relative to WT mice in basal conditions.
Changes in cortical structure occurring in WT mice had not recovered 19 weeks
after BtxA injection, despite correction of the early osteoclast activation and
a modest increase in periosteal bone formation. Thus, BtxA-induced muscle
paralysis leads to rapid loss of trabecular bone and to changes in structural
and biomechanical properties of cortical bone, neither of which are fully
reversed after 19 weeks. Osteoblast/osteocyte Cx43 is involved in the adaptive
responses to skeletal unloading selectively in the cortical bone, via modulation
of osteoclastogenesis on the endocortical surface.
A series of 178 immediate reconstructions with regional or distant tissue for repair of oropharyngeal defects caused by treatment of head and neck cancer was reviewed to determine whether reconstruction with free flaps was more or less expensive than reconstruction with regional myocutaneous flaps. In this series, three types of flaps were used: the radial forearm free flap (n = 89), the rectus abdominis free flap (n = 56), and the pectoralis major myocutaneous flap (n = 33). Resource costs were determined by adding all costs to the institution of providing each service studied using salaried employees (including physicians). The two free-flap groups were combined to compare free flaps with the pectoralis major myocutaneous flap, a regional myocutaneous flap. Failure rates in the two groups were similar (3.0 percent for pectoralis major myocutaneous flap, 3.4 percent for free flaps). The mean costs of surgery were slightly higher for the free flaps, but the subsequent hospital stay costs were lower. Therefore, the total mean resource cost for the free-flap group ($28,460) was lower than the cost for the myocutaneous flap group ($40,992). The pectoralis major myocutaneous flap may have been selected for more patients with advanced disease and systemic medical problems, contributing to longer hospitalization and added cost. Nevertheless, this study suggests that free flaps are not more expensive than other methods and may provide cost savings for selected patients.
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