Novel genetic mutation associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome treated with denosumab: a case report.

In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.

Gamma-delta T lymphocytes and 25-hydroxy vitamin D levels as key factors in autoimmunity and inflammation: the case of zoledronic acid-induced acute phase reaction.

Zoledronic acid (ZA) infusion for osteoporosis is frequently associated with the onset of an acute phase reaction (APR) secondary to the activation of γδ T cell receptor (TCR) lymphocytes (γδ T cells) and to low vitamin D levels, similar to what is observed in chronic inflammation and autoimmunity. In this study we investigated whether the phenotype of γδ T cells is associated with APR and 25-OH vitamin D (25-OHvD) levels. For flow-cytometry analysis, peripheral blood samples were obtained from 52 osteoporotic women prior to 5 mg ZA intravenous infusion and from nine women (five with APR) one week later. Twenty-six/52 (50%) patients reported APR and APR+ cases had a higher percentage of central memory Th1-like γδ T cells. One week after ZA infusion, APR was associated with a decreased percentage of central memory Th1-like γδ T cells, an increase in the percentage and activation of effector memory Th1-like γδ T cells, and an increase in Th17-like γδ T cells. Lower 25-OHvD levels were significantly associated with APR, but no correlation was found between 25-OHvD level and γδ T cell percentage or subsets. In conclusion, patients experiencing APR related to ZA infusion have lower 25-OHvD levels and we suggest that the higher percentage of central memory Th1-like γδ T cells and the expansion of effector memory Th1-like and Th17-like γδ T cells are associated with the occurrence of APR.

Circulating immature osteoprogenitor cells and arterial stiffening in postmenopausal osteoporosis.

BACKGROUND AND AIMS: An increased number of circulating osteoprogenitor cells (OPCs) expressing bone-related proteins and the stem cell marker CD34 have been identified in women with postmenopausal osteoporosis, who also have stiffer arteries than nonosteoporotic subjects. We investigated whether an increased number of circulating OPCs underlies the association of osteoporosis with arterial stiffness. METHODS AND RESULTS: The number of circulating OPCs was quantified by FACS analysis in 120 postmenopausal women with or without osteoporosis. OPCs were defined as CD34+/alkaline phosphatase(AP)+ or CD34+/osteocalcin(OCN)+ cells. Participants underwent cardiovascular risk factor assessment, measurement of bone mineral density (BMD), and aortic pulse wave velocity (aPWV) as a measure of arterial stiffness. Osteoporotic women had higher aPWV (9.8 ± 2.8 vs 8.5 ± 1.9 m/s, p = 0.005) and levels of CD34+/AP+ and CD34+/OCN+ cells than nonosteoporotic controls [1045 n/mL (487-2300) vs 510 n/mL (202-940), p < 0.001; 2415 n/mL (1225-8090) vs 1395 n/mL (207-2220), p < 0.001]. aPWV was associated with log-CD34+/AP+ (r = 0.27, p = 0.003), log-CD34+/OCN+ cells (r = 0.38, p < 0.001). In stepwise regression analysis CD34+/OCN+ cells, age, systolic blood pressure and heart rate were significant predictors of aPWV (Model R = 0.62, p < 0.001), independent of cardiovascular risk factors, parathyroid hormone levels and osteoporotic status. CONCLUSION: In women with postmenopausal osteoporosis an increased availability of circulating osteoprogenitor cells has a detrimental influence on arterial compliance, which may in part explain the association between osteoporosis and arterial stiffening.

Association between circulating osteoprogenitor cell numbers and bone mineral density in postmenopausal osteoporosis.

UNLABELLED: The role of circulating osteoprogenitor cells in postmenopausal osteoporosis is unknown. We found that alkaline-phosphatase-positive (AP+) cells are the lacking cells in osteoporosis, whose reduction is related to bone loss. Conversely, the increased number of alkaline phosphatase/CD34-positive cells may reflect the reactive bone marrow contribution to bone formation. INTRODUCTION: Circulating osteoprogenitor cells mineralize in vitro and in vivo. Loss of osteogenic cells may account for bone loss in osteoporosis. We studied whether there is an association between the number of circulating osteoprogenitor cells and bone mineral density (BMD) in postmenopausal women with and without osteoporosis. METHODS: The number of circulating AP+, osteocalcin-positive (OCN+), AP+/CD34+, and OCN+/CD34+ cells was quantified in 54 postmenopausal osteoporotic women and 36 age-matched nonosteoporotic controls. RESULTS: The number of AP+ cells was lower in osteoporotic women than in controls (127 +/- 16 vs 234 +/- 23 per microliter; p < 0.001); higher levels of AP+/CD34+, OCN+, and OCN+/CD34+ cells were found in osteoporotic than controls (p < 0.01 for all). The number of AP+ cells was correlated with lumbar BMD (rho = 0.29; p = 0.008) and proximal femur BMD (rho = 0.31; p = 0.005) whereas inverse correlations were found between AP+/CD34+ cells, OCN+, OCN+/CD34+, and BMD. Reduced AP+ cells and increased AP+/CD34 +, OCN+, and OCN+/CD34+ cells were predictors of low BMD, independent of traditional risk factors for osteoporosis. CONCLUSION: In postmenopausal osteoporotic women, a reduced number of circulating AP+ cells and increased levels of AP+/CD34+, OCN+, and OCN+/CD34+ cells are associated with reduced bone mineral density, the interpretation of such a cellular imbalance needing exploration.