tetracycline and Osteopetrosis

The aim of this study was to evaluate the value of the urinary excretion of the pyridinium crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), as markers of bone resorption in the rat. The excretion of the crosslinks was compared with that of urinary [3H]tetracycline ([3H]TC) excretion from chronically [3H]TC-prelabeled animals, a technique established to monitor bone resorption in the rat. Bone resorption was modulated by Ca restriction, infusion of PTH, thyroparathyroidectomy, and administration of different bisphosphonates. Furthermore, the urinary crosslinks were assessed in three different osteopetrotic mutations in the rat. We found a delayed response of Pyr and D-Pyr excretion to acute changes in bone resorption compared with [3H]TC excretion. This delay was 1 day after Ca restriction and longer after other treatments, such as PTH administration or bisphosphonate treatment, with which it was more than 3 weeks. In contrast, chronic states with stimulation or inhibition of bone resorption showed similar changes in excretion of the urinary crosslinks and [3H]TC, except after PTH administration. The excretion of the crosslinks was greatly reduced in osteopetrotic rats (op/op, tl/tl, and ia/ia) and increased to normal levels in tl/tl rats after stimulation of bone resorption by M-CSF administration. These results suggest that, in rats, urinary excretion of the pyridinium crosslinks reflects bone resorption in chronic but not always in acute conditions. The cause of this discrepancy is still unclear.

Topics: Amino Acids; Animals; Biomarkers; Bone and Bones; Bone Resorption; Diphosphonates; Male; Osteopetrosis; Rats; Rats, Wistar; Tetracycline

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Biopsy; Bone Resorption; Female; Histological Techniques; Humans; Ilium; Male; Middle Aged; Osteogenesis; Osteopetrosis; Radiography; Tetracycline

Topics: Ammonium Chloride; Anemia; Anemia, Hemolytic; Blood Transfusion; Bone Development; Calcium; Calcium, Dietary; Child; Diet; Diet Therapy; Humans; Infant; Osteopetrosis; Parathyroid Hormone; Phosphates; Prednisolone; Radiography; Tetracycline

Osteopetrosis was experimentally produced and lesion development in time was studied by fluorescent illumination of tetracycline labels in the bone. Bones from birds 84, 115, 186 and 354 days of age were examined by ground section under ultraviolet light. Periosteal activity of the tibia and femur was present in normal bones at 84 days of age but had stopped at 115 days. Focal periosteal activity of osteopetrotic lesions was present at 186 days but not at 354 days of age. Slight endosteal activity of osteopetrotic bones was present at 354 days of age. Osteopetrotic bone formed at a rate of 1.26 mm. per week or 6 times faster than normal bone in some of these lesions. Tetracycline diffused throughout the 354-day-old osteopetrotic lesion but not normal compact bone indicating that the osteopetrotic bone is porous and spongy.

Topics: Animals; Fluorescence; In Vitro Techniques; Osteopetrosis; Poultry Diseases; Tetracycline