Postnatal skeletal stem cells.

Postnatal skeletal stem cells are a subpopulation of the bone marrow stromal cell network. To date, the most straightforward way of assessing the activity of skeletal stem cells within the bone marrow stromal cell (BMSC) population is via analysis of the rapidly adherent, colony-forming unit-fibroblast (CFU-F), and their progeny, BMSCs. Several in vitro methods are employed to determine the differentiation capacity of BMSCs, using osteogenic and adipogenic "cocktails" and staining protocols, and pellet cell culture for chondrogenic differentiation. However, true differentiation potential is best determined by in vivo transplantation in either closed or open systems. By in vivo transplantation, approximately 10% of the clonal strains are able to form bone, stroma, and marrow adipocytes, and are true skeletal stem cells. Furthermore, when derived from patients or animal models with abnormalities in gene expression, they recapitulate the disease phenotype on in vivo transplantation. Although ex vivo expansion of BMSCs inevitably dilutes the skeletal stem cells, when used en masse, they are attractive candidates for reconstruction of segmental bone defects, and as targets for gene therapy.

Monostotic fibrous dysplasia of the proximal femur and liposclerosing myxofibrous tumor: which one is which?

Clinical, histological, and genetic studies of two cases of isolated fibro-osseous lesions of the femur in adults show the overlap between monostotic fibrous dysplasia (MFD) of the proximal femur and the so-called liposclerosing myxofibrous tumor. The two cases highlight how the incomplete understanding of the natural history of MFD may result in diagnostic pitfalls or incorrect classification of individual lesions.

Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone.

Fibrous dysplasia of bone (FD) is a congenital, non-heritable skeletal disorder that is associated with multiple skeletal complications, including repeated fractures, limb length discrepancy, and bone pain. The disease-specific impact of FD on quality of life outcomes is unknown. We sought to understand the impact of the scope and extent of the skeletal disease on quality of life in adults and children with FD. The health-related quality of life was quantified in a population of adults (n = 56) and children (n = 22) with FD using validated health assessment questionnaires, the Medical Outcomes Study 36 Item Short-Form Health Survey, volume 2 (SF36) (adults) and the Child Health Questionnaire Parent Form 50 (CHQ-PF50) (children). Clinical demographic data and skeletal disease burden scores (SDBS, amount of skeleton involved with FD) were measured, and correlations with health-related quality of life were sought. The SF36 and CHQ-PF50 revealed lower Physical Function Summary scores in FD patients compared to the U.S. population norms (adult 41 vs. 50, Z score < -5.0, pediatric 39 vs. 50, Z score < -5.0). However, the SF36 and CHQ-PF50 Mental/Psychological summary scores were not different from those of U.S. population norms (adult 50 vs. 50, Z score = 0, pediatric 48 vs. 50 Z score = -0.9). The score on the Physical Function Domain of both tools was strongly negatively associated with the SDBS (adult Spearman rho = -0.43, P = 0.009, pediatric Spearman rho = -0.72, P = 0.005). The groups of adult and pediatric patients with SDBS > 30 had decreased Physical Function Domain scores when compared to those with scores < 30 (adult 35 vs. 45, P = 0.002, pediatric 57 vs. 78, P = 0.04, respectively). One of the largest effects was seen in the parents of children with FD, who had significantly lower Parental Emotional scores than those of the parents of healthy norms (54 vs. 88, Z score < -5.0), suggesting a high degree of emotional morbidity in the parents of children with FD. Despite measurable functional limitations in adults and children, and significant parental emotional impairment, patients with FD achieve a high level of social and emotional function. These data are important for prognosis and parental reassurance.

FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.

FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified "fibrous" cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.