Reply: The ultimate goal of research in fibrodysplasia ossificans progressiva (FOP) is the development of treatments that will prevent, halt, or even reverse the progression of the condition. The rational scientific basis for bone marrow transplantation in the treatment of FOP was first suggested by studies that showed overexpression of bone morphogenetic protein-4 (BMP-4) in FOP lymphocytes7 and the presence of lymphocytes in the earliest FOP lesions.4 The argument for bone marrow transplantation for the treatment of FOP has been strengthened most recently by studies showing the global disruption of the BMP-4 pathway in FOP lymphoblastoid cells (LCLs).1 A set of articles published 2 years ago in Clinical Orthopaedics & Related Research discussed the pros and cons of bone marrow transplantation for the treatment of FOP.2,3 In a new letter, Altschuler refers to an old and infrequently cited 1983 case report of a patient with aplastic anemia and myositis ossificans progressiva (now referred to as fibrodysplasia ossificans progressiva) who had a second bone marrow transplantation after an initial unsuccessful transplantation and experienced “no further deterioration in his mobility” for 2½ years after the second transplantation.8 Altschuler cites the old case as an endorsement for bone marrow transplantation in the treatment of FOP. The endorsement is enthusiastic, but we think it is premature. The original treating physicians have tried valiantly to locate the patient to reassess his disease 23 years after the transplant, but so far have not been able to do so. Such an assessment obviously would be of inestimable value. Clinicians who work extensively with patients who have FOP will recognize that the medical literature is replete with anecdotal case reports citing short-term benefits of one therapy or another. As Julius Rosenstirn stated nearly a century ago, “The disease (fibrodysplasia ossificans progressiva) was attacked with all sorts of remedies and alternatives for faulty metabolism; every one of them with more or less marked success observed solely by its original author but pronounced a complete failure by every other follower. In many cases, the symptoms of the disease disappeared often spontaneously, so that the therapeutic effect should not be unreservedly endorsed.”6 Our group observes more than 400 patients with FOP worldwide, and we commonly see that early FOP flareups resolve spontaneously and that disease progression may cease for years or decades without additional progression.5 The reported followup on the case cited by Altschuler is insufficient for an endorsement of bone marrow transplantation for FOP, but provides an important opportunity for long-term followup that could strengthen the case for a therapeutic benefit in bone marrow transplantation. Experiments are underway in our laboratory to use an in vivo mouse model to reproduce the pathophysiology of FOP lesions using marrow-derived stem cells from patients who have FOP. If successful in creating a more robust animal model of the disease, the logical extension will be to use allogenic bone marrow transplantation to arrest the progression of the condition. It may even become possible to successfully remove heterotopic bone under the protection of a successful bone marrow transplantation. Recent advances in stem cell biology now bring us a step closer to an effective treatment. The case cited by Altschuler lacks long-term followup, but provides the opportunity to look back at a coincidental treatment destined for a rendezvous with evolving scientific rationale. Frederick S. Kaplan, MD Department of Orthopaedic Surgery,, The University of Pennsylvania School of Medicine,, Philadelphia, PA; and the Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA David L. Glaser, MD Department of Orthopaedic Surgery,, The University of Pennsylvania School of Medicine, Philadelphia, PA Eileen M. Shore, PhD Department of Orthopaedic Surgery,, The University of Pennsylvania School of Medicine, Philadelphia, PA; and the Department of Genetics, The University of Pennsylvania School of Medicine, Philadelphia, PA Stephen G. Emerson, MD, PhD Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA