Effects of Parathyroid Hormone on Cancellous Bone Mass and Structure in Osteoporosis

2004 ◽  
Vol 10 (21) ◽  
pp. 2615-2627 ◽  
Author(s):  
Naohisa Miyakoshi
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
Cancellous Bone

scholarly journals RAGE supports parathyroid hormone-induced gains in femoral trabecular bone

2010 ◽  
Vol 298 (3) ◽  
pp. E714-E725 ◽  
Author(s):  
Binu K. Philip ◽  
Paul J. Childress ◽  
Alexander G. Robling ◽  
Aaron Heller ◽  
Peter P. Nawroth ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
Bone Mineral ◽  
Cancellous Bone ◽  
Immunoglobulin Superfamily ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Bone Response ◽  
Accrual Rate ◽  
Underlying Mechanisms

Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but significant questions remain as to the underlying mechanisms. The receptor for advanced glycation end products (RAGE) is a multiligand receptor of the immunoglobulin superfamily; however, recent studies indicate a role in bone physiology. We investigated the significance of RAGE to hormone-induced increases in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice with human PTH-(1–34) at 30 μg·kg−1·day−1 or vehicle control, 7 days/wk, for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD) and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH-mediated relative increases in cortical area of the midshaft femur were not compromised in the null mice. However, the hormone-induced gain in femoral cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE impaired PTH-mediated increases in femoral cancellous bone volume, connectivity density, and trabecular number but did not impact increases in trabecular thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral expression of bone formation genes, but their relative PTH-responsiveness was not impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass, with the exception of the spine, and an enhanced accrual rate of fat mass. We conclude that RAGE is necessary for key aspects of the skeleton's response to anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of femoral trabecular architecture but not intrinsically necessary for increasing cortical thickness.

Parathyroid hormone is predictive of low bone mass in Canadian Aboriginal and White women

Bone ◽  
2008 ◽  
Vol 42 (3) ◽  
pp. 498-504 ◽  
Author(s):  
Hope A. Weiler ◽  
William. D. Leslie ◽  
Charles N. Bernstein
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
White Women ◽  
Low Bone Mass

scholarly journals Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2132-2140 ◽  
Author(s):  
Keiichiro Kitahara ◽  
Muneaki Ishijima ◽  
Susan R. Rittling ◽  
Kunikazu Tsuji ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Wild Type ◽  
Mineral Density ◽  
Cortical Bone Mass ◽  
Intermittent Pth

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

scholarly journals Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Mass Density ◽  
Female Rats ◽  
Bone Mass Density ◽  
Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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