title: Modifications in bone matrix of estrogen-deficient rats treated with intermittent PTH.
abstract: Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.
authors.affiliation: Department of Morphology and Genetics, School of Medicine, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil ; Mineralized Tissue and Histology Research Laboratory, Department of Morphology and Genetics, Federal University of São Paulo School of Medicine (UNIFESP), Rua Botucatu, 740 Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Rafael
authors.identifier: 0000-0001-7259-079X
authors.initials: R
authors.lastname: Pacheco-Costa
authors.affiliation: Department of Morphology and Genetics, School of Medicine, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil ; Mineralized Tissue and Histology Research Laboratory, Department of Morphology and Genetics, Federal University of São Paulo School of Medicine (UNIFESP), Rua Botucatu, 740 Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Jenifer Freitas
authors.initials: JF
authors.lastname: Campos
authors.affiliation: Department of Morphology and Genetics, School of Medicine, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil ; Mineralized Tissue and Histology Research Laboratory, Department of Morphology and Genetics, Federal University of São Paulo School of Medicine (UNIFESP), Rua Botucatu, 740 Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Katchburian
authors.affiliation: Department of Biochemistry, School of Medicine, Federal University of São Paulo, 04044-020 São Paulo, SP, Brazil.
authors.forename: Valquíria Pereira
authors.initials: VP
authors.lastname: de Medeiros
authors.affiliation: Department of Biochemistry, School of Medicine, Federal University of São Paulo, 04044-020 São Paulo, SP, Brazil.
authors.forename: Helena Bonciani
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Keico Okino
authors.initials: KO
authors.lastname: Nonaka
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA.
authors.forename: Lilian Irene
authors.initials: LI
authors.lastname: Plotkin
authors.affiliation: Department of Morphology and Genetics, School of Medicine, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil ; Mineralized Tissue and Histology Research Laboratory, Department of Morphology and Genetics, Federal University of São Paulo School of Medicine (UNIFESP), Rua Botucatu, 740 Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Rejane Daniele
authors.initials: RD
authors.lastname: Reginato
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001857:Bone Matrix / Q000187:drug effects* / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
chemical_list: D004967:Estrogens; D010281:Parathyroid Hormone; D002809:Chondroitin Sulfates; D003094:Collagen