Fat grafts transplanted into surgically created bone defects inhibit local bone regeneration. This phenomenon is employed to good effect by surgeons. In neurosurgery, fat grafts prevent constriction of the spinal cord by laminectomy membrane composed of scar tissue and bony callus. Also, following the resection of a seg- ment of ulnar diaphysis or a transphyseal bone bridge in growing dogs and children, the inser- tion of a fat graft prevents the local regener- ation of bone; effectively producing a localised atrophic non-union and allowing continued bone growth (1,2). Since fat grafts are composed mainly of adipocytes embedded in a sparse fibrous stroma, it has been assumed that a piece of fat filling a bony void simply prevents the ingrowth of fibrovascular tissue and subse- quent bone callus formation. As orthopaedic surgeons, this appreciation Mechanical loading is a very major factor regulating bone remodelling in skeletally ma- ture animals, but leptin also has some role in regulating bone mass. Leptin acts directly on bone cells and bone marrow stem cells, and indirectly via the hypothalamic-sympathetic nervous system to alter bone mass (4). Leptin receptors are present in the hypothalamus, and receptor-bound leptin blocks sympath- etic innervation of bone. Sympathetic nerve fibres are widely and non-uniformly dis- tributed over bone surfaces, and normally the release of noradrenaline from sympathetic fibres projecting onto bone inhibits bone formation. Thus elevated levels of leptin may act centrally, and indirectly result in bone proliferation. Although these interactions are quite complex, a growing body of knowledge provides us with a whole new window of in- sight into the understanding the 'non- loading' mechanisms that control bone re- modelling. These neuro-endocrine mech- anisms are probably important in regulating normal bone remodelling in 'non-loaded' limb bones such as the upper limb in bipedal animals. Also, they might be involved in the development of certain idiopathic bone dis- eases. For example, animals and people suf- fering from secondary hypertrophic oste- opathy (Marie's Disease) have bilaterally symmetrical periosteal bone formed along the diaphyses of the limb bones, in conjunc- tion with intra-thoracic pathology. Often the bone proliferation on the limbs will inexplic- ably regress after resection of the intra-tho- racic lesion, suggesting that some type of neuro-endocrine mechanism is responsible for the bone proliferation. Certainly it is grat- ifying to appreciate how research into the growing epidemic of obesity has serendipi- tously revealed so much new knowledge about the regulation of bone remodelling.