Biomedical subjects

M Priemel

Publications and source records attributed to M Priemel.

23 records · Page 2Linked to original sources

PubMed1999

The Gorham-Stout syndrome (Gorham's massive osteolysis). A report of six cases with histopathological findings.

The Gorham-Stout Syndrome (Gorham's massive osteolysis) is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report six cases of the condition and present evidence that osteolysis is due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy such as with calcitonin or bisphosphonates may prevent local progressive osteolysis.

Adult↗

PubMed1999

Severe osteoporosis in familial Hajdu-Cheney syndrome: progression of acro-osteolysis and osteoporosis during long-term follow-up.

Hajdu-Cheney syndrome is an autosomal dominant inherited osteodysplastic bone disease with the hallmarks of acro-osteolysis, skull deformations, and generalized osteoporosis. Very few patients have been followed long-term with respect to the prognosis of acro-osteolysis and osteoporosis. Here we describe a 39-year-old woman and her 19-year-old daughter who are both affected with the Hajdu-Cheney syndrome. Skeletal lesions were followed in the mother between the ages of 22 and 39 years. The acro-osteolytic lesions progressed markedly and caused shortening of several fingers; some end phalanges had completely disappeared. Severe spinal osteoporosis with serial vertebral fractures was found at the age of 22 years. New vertebral fractures developed until the age of 33 years, but did not progress afterward. High turnover osteoporosis was found in the bone histology of iliac crest biopsies performed at the ages of 22 and 34 years. Bone mineral content (BMC) was strikingly decreased at the age of 34 years (T score -5.1 SD) and did not significantly change during further follow-up. In the daughter, BMC failed to increase between the ages of 12 and 19 years and was also markedly decreased (T score -4.4 SD). This suggests that osteoporosis in Hajdu-Cheney syndrome is related to a low peak bone mass and a high bone turnover, leading to insufficient bone formation compared with the increased bone resorption.

Adult↗

PubMed1998

Dissociation between bone resorption and bone formation in osteopenic transgenic mice.

Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo.

Animals↗

PubMed1998

Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice.

1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.

Alopecia↗

PubMed1998

PTHrP and Bcl-2: essential regulatory molecules in chondrocyte differentiation and chondrogenic tumors.

Human chondrosarcomas (CS) are a frequent form of malignant bone tumors. The accurate distinction between benign solitary enchondroma and conventional CS of bones is a major diagnostic goal. Although the histological characteristics of chondrogenic tumors and the grading of CS (G1 to G3) have been defined by several authors, immunohistochemical markers for the different entities and grades are still missing and the mechanisms of tumorigenesis remain poorly understood. In addition to the emerging evidence that parathyroid hormone-related peptide (PTHrP) plays a critical role in endochondral bone formation we have recently reported that Bcl-2 lies downstream of PTHrP in the regulation of chondrocyte differentiation. To further characterize chondrogenic tumors and to determine whether PTHrP and the regulation of Bcl-2-expression is of relevance to tumorigenesis, we analyzed the expression of both PTHrP and Bcl-2 on a series of 23 cases of solitary enchondroma (9 cases) and primary CS (14 cases) using light and confocal microscopy. While all 9 enchondromas exhibited a detectable level of PTHrP-expression only, 2 showed low levels of immunoreactivity for Bcl-2. In sharp contrast, strong coexpression of Bcl-2 and PTHrP was found in 11 (composed of 3 CS G3, 7 CS G2, and one dedifferentiated CS) out of 14 CS, while the expression level of these proteins was below the detection limit in two CS G1 and one dedifferentiated CS. To verify this data 3 cases each of enchondroma, CS G2, and CS G3 respectively, were subjected to quantitative confocal analysis, after double labeling for PTHrP and Bcl-2. The results showed a significant increase in the expression of both PTHrP and Bcl-2, in malignant CS versus the benign enchondromas. Most interestingly, the levels of expression of both PTHrP and Bcl-2 correlated with the degree of malignancy of the chondrogenic tumors. These results therefore suggest that both PTHrP and Bcl-2 play a role in the tumorigenesis of chondrogenic tumors and further indicate that both proteins may participate in the same pathway regulating chondrocyte differentiation.

Adult↗