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Simple bone cysts are common benign lesions in growing children that predispose them to fracture and are sometimes painful. The purpose of this trial was to compare rates of healing of simple bone cysts treated with intralesional injections of bone marrow with rates of healing of those treated with methylprednisolone acetate.Of ninety patients randomly allocated to treatment with either a bone-marrow or a methylprednisolone acetate injection, seventy-seven were followed for two years. The primary outcome, determined by a radiologist who was blind to the type of treatment, was radiographic evidence of healing. The cyst was judged to be either not healed (grade 1 [a clearly visible cyst] or grade 2 [a cyst that was visible but multilocular and opaque]) or healed (grade 3 [sclerosis around or within a partially visible cyst] or grade 4 [complete healing with obliteration of the cyst]). Patient function was assessed with use of the Activity Scale for Kids, and pain was assessed with the Oucher Scale.Sixteen (42%) of the thirty-eight cysts treated with methylprednisolone acetate healed, and nine (23%) of the thirty-nine cysts treated with bone marrow healed (p = 0.01). There was no significant difference between the treatment groups (p > 0.09) with respect to function, pain, number of injections, additional fractures, or complications.Although the rate of healing of simple bone cysts was low following injection of either bone marrow or methylprednisolone, the latter provided superior healing rates.Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.