Anabolic Actions of Parathyroid Hormone on Bone*

Dempster, David W.; Cosman, Felicia; Parisien, May; Shen, Victor; Lindsay, Robert

doi:10.1210/edrv-14-6-690

Cited by 439 publications

(542 citation statements)

References 165 publications

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“…Previous studies have indicated that intermittent or pulsatile PTH treatment is known to markedly increase trabecular bone volume owing to a dominant stimulation of trabecular bone formation and to cause a small loss of cortical bone. (12,13) Here, we demonstrate that both short-and long-term treatment with intermittent PTH after marrow ablation induces the sequential formation of new bone, first intramedullary and then endosteal. Indeed, PTH continues to increase the bone-formation rate after 84 days of treatment.…”

Section: Discussionmentioning

confidence: 76%

Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats

Zhang

Carlson

et al. 2010

Journal of Bone and Mineral Research

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We previously reported that following mechanical ablation of the marrow from the midshaft of rat femurs, there is a rapid and abundant but transient growth of bone, and this growth is enhanced and maintained over a 3-week period by the bone anabolic hormone parathyroid hormone (PTH). Here, we asked whether further treatment with PTH or bisphosphonates can extend the halflife of the new bone formed in lieu of marrow. We subjected the left femur of rats to mechanical marrow ablation and treated the animals 5 days a week with PTH for 3 weeks (or with vehicle as a control) to replace the marrow by bone. Some rats were euthanized and used as positive controls or treated with vehicle, PTH, or the bisphosphonate alendronate for a further 9 weeks. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography (pQCT), micro-computed tomography (mCT), dynamic histomorphometry analysis, and biomechanical testing. We also determined the concentrations of serum osteocalcin to confirm the efficacy of PTH. Treatment with PTH for 3 months dramatically enhanced endosteal and periosteal bone formation, leading to a 30% increase in cortical thickness. In contrast, alendronate protected the bone that had formed in the femoral marrow cavity after marrow ablation and 3 weeks of treatment with PTH but failed to promote endosteal bone growth or to improve the biomechanical properties of ablated femurs. We further asked whether calcium-phosphate cements could potentiate the formation of bone after marrow ablation. Marrow cavities from ablated femurs were filled with one of two calcium-phosphate cements, and rats were treated with PTH or PBS for 84 days. Both cements helped to protect the new bone formed after ablation. To some extent, they promoted the formation of bone after ablation, even in the absence of any anabolic hormone. Our data therefore expand the role of PTH in bone engineering and open new avenues of investigation to the field of regenerative medicine and tissue engineering. Local bone marrow aspiration in conjunction with an anabolic agent, a bisphosphonate, or a calcium-phosphate cement might provide a new platform for rapid preferential site-directed bone growth in areas of high bone loss. ß

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Section: Discussionmentioning

confidence: 76%

Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats

Zhang

Carlson

et al. 2010

Journal of Bone and Mineral Research

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“…No significant changes in bone resporption, indicated by s-CTX, were found in either group. Because PTH increases bone turnover in general, it is not uncommon that bone formation also increases, and intermittent administration of PTH is known to increase bone formation more than it increases resorption, thus increasing bone mass (for review, see Dempster et al, 1993). Why bone formation increased in the C group is not clear.…”

Section: Discussionmentioning

confidence: 99%

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects

et al. 2005

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Background: Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss. Objective: We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism. Design: A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low-salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed. Results: The LS group showed a significant decline (P ¼ 0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P ¼ 0.03). The C group showed an increase in s-PTH (P ¼ 0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism. Conclusions: We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism. Sponsorship: The study was supported by Tekes-National Technology Agency of Finland.

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“…Since then, this cortical steal phenomenon has been widely studied. (6) In primates, it has been shown that intermittent PTH 1-34 or PTH 1-84 exposure causes an increase in cortical porosity. (7,8) This was, however, shown not to decrease integral bone strength, as the pores were preferentially located near the endosteal surface, where their biomechanical impact was limited, and this effect was outweighed as treatment also increased the cortical area.…”

Section: Introductionmentioning

confidence: 99%

Differing effects of PTH 1–34, PTH 1–84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: An 18-month open-labeled observational study using HR-pQCT

Hansen¹,

Hauge²,

Jensen³

et al. 2012

Journal of Bone and Mineral Research

137

100

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Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used highresolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 mg sc daily, n ¼ 18) or PTH 1-84 (100 mg sc daily, n ¼ 20) for 18 months in an open-label, nonrandomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n ¼ 33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 AE 37%, PTH 1-84 39 AE 32%, both p < 0.001) and tibia (PTH 1-34 13 AE 27%, PTH 1-84 15 AE 22%, both p < 0.001) with corresponding declines in cortical density. With PTH 1-34, increases in cortical thickness in radius (2.0 AE 3.8%, p < 0.05) and tibia (3.8 AE 10.4%, p < 0.01) were found. Trabecular number increased in tibia with both PTH 1-34 (4.2 AE 7.1%, p < 0.05) and PTH 1-84 (5.3 AE 8.3%, p < 0.01). Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3.0 AE 3.5%, p < 0.01), total (2.7 AE 2.5%, p < 0.001) and cortical density (1.5 AE 2.0%, p < 0.01) in tibia as well as trabecular volume fraction in radius (2.5 AE 5.1%, p < 0.05) and tibia (2.2 AE 2.2%, p < 0.01). FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (À2.8 AE 5.8%, p < 0.05) and tibia (-3.9 AE 4.8%, p < 0.001). Conclusively, divergent treatment-specific effects in cortical and trabecular bone were observed with anabolic and zoledronic acid therapy. The finding of decreased estimated strength with PTH 1-84 treatment was surprising and warrants confirmation. ß

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Anabolic Actions of Parathyroid Hormone on Bone*

Cited by 439 publications

References 165 publications

Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats

Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects

Differing effects of PTH 1–34, PTH 1–84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: An 18-month open-labeled observational study using HR-pQCT

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