Hormone therapy could enhance the therapeutic effect of head and facial bone grafts

Bone grafts, which are used to treat head injuries and birth defects, still pose major medical challenges, but scientists are reporting progress toward a new hormone therapy that could improve the outcomes of these surgeries. Their study, which was conducted on mice, appears in the ACS journal Molecular Pharmaceutics.

Zulma Gazit at Cedars-Sinai Medical Center, Edward Schwarz from Rochester University and colleagues note that surgeons perform nearly 100,000 head and facial bone-grafting procedures every year to treat bone loss from disease, birth defects or traumatic injuries. Though this kind of reconstructive surgery dates back to ancient times, the options for implant materials remain limited. Doctors can remove bone from another part of a patient’s body or use lab-made materials, but these methods can lead to serious complications. Currently, one of the preferred alternatives is to use bone grafts received from tissue banks, but they often don’t join with the bone they’re supposed to fix. Preliminary studies have shown that parathyroid hormone (PTH), a drug approved by the U.S. Food and Drug Administration to treat osteoporosis, helps repair fractures in long bones. The team wanted to see if PTH also would help head and facial donor grafts fuse into place.

They tested the hormone in mice with skull defects that they implanted with donor grafts. Daily short-term PTH treatment improved bone formation around the grafts and prevented scar tissue, which can interfere with graft integration, from forming. “These findings will aid in the development of an attractive bone graft, which is readily available, for use in craniofacial reconstruction,” they say.

The authors acknowledge funding from the U.S. National Institute of Dental and Craniofacial Research (grant number DE019902).

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Bone defects in the craniomaxillofacial skeleton vary from the small (few millimeters) periodontal defects to the large segmental defects resulting from trauma, surgical excision, or cranioplasty. Such defects typically have complex three-dimensional structural needs, which are difficult to restore. In cranial vault defects, the underlying brain needs permanent protection. Segmental jaw defects require restoration of mechanical integrity, temporomandibular joint function, and intermaxillary dental occlusion. Maintaining acceptable facial esthetics is another unique consideration in the treatment of facial defects, which cannot be underestimated. Bone grafts remain the gold standard for reconstructing segmental bone defects. We will overview the status of bone grafting techniques for craniofacial reconstruction, their biological foundation, as well as future directions.

The earliest report of a bone grafting procedure came in an 1682 book by Job Janszoo van Meekeren, a surgeon in Amsterdam. In this account, the author reported a case in Russia, where the surgeon restored a cranial defect using a cranial bone graft from a dead dog. In 1881, Sir William MacEwen of Rothesay, Scotland, published the first case report of successful interhuman transfer of bone grafts. He used tibial bone wedges excised from three donors, during surgical correction of skeletal deformity, to reconstruct a humeral defect in a 3-year-old child. Subsequent clinical reports helped establish the efficacy of autogenous bone grafts in defect reconstruction.


A bone graft is defined as any implanted material that promotes bone healing, whether alone or in combination with other material. Augmentation of bone healing at the recipient site occurs through one or more of the following mechanisms: osteoconduction, osteoinduction, and osteogenesis. An osteoconductive material simply allows, or directs, new bone formation along its surfaces. Examples include bone graft matrix and synthetic osteoconductive polymers. An osteoinductive graft supplies recruitment and/or differentiation factors for bone-forming cells at the recipient site.

An osteogenic graft supplies induced, or inducible, bone-forming cells to the recipient site. Accordingly, an ideal bone graft is the one that functions through all three mechanisms by providing a template that directs three-dimensional bone growth (osteoconduction), recruits and induces differentiation of resident bone-forming cells, and supplies more bone-forming cells to the recipient site. Such grafts include cancellous and vascularized bone grafts.

Bone grafts can be employed for functions other than to stimulate bone formation within a defect. An onlay graft laid over facial bone surfaces could augment the cheek prominence or restore facial contour. In this case, more emphasis is directed toward the rate of graft resorption. Those grafts that are known for their slow resorption, such as calvarial and cortical bone, or nonresorption, such as synthetic materials, are preferred. Such grafts might also be used for their mechanical properties wherever mechanical support or immediate protection of vital structures is required, as in reconstructing orbital floor or calvarial defects.

Slow resorption is a disadvantage if the graft is used to augment bone formation at the recipient site. Graft incorporation is inversely proportional to how solid the graft is and how slow it resorbs. Therefore, osteoconductive graft materials with interconnected internal spaces that reach the outer surface are better scaffolds for directing three-dimensional bone invasion of the graft. This architecture provides more surface area along which native osteoclasts can attach themselves and start dissolving the graft, which is the first stage in graft incorporation.

Michael Bernstein
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American Chemical Society

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