Both hPTH(1-34) and bFGF Increase Trabecular Bone Mass in Osteopenic Rats but They Have Different Effects on Trabecular Bone Architecture

Nancy E Lane, Wei Yao, John H. Kinney, Gunnard Modin, Mehdi Balooch, Thomas J. Wronski

    Research output: Contribution to journalArticle

    80 Citations (Scopus)

    Abstract

    Osteoporosis is a syndrome of excessive skeletal fragility that results from both the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF has been found to increase trabecular bone mass in osteoporotic rats. The purpose of this study was to compare how trabecular bone architecture, bone cell activity, and strength are altered by two different bone anabolic agents, bFGF and hPTH(1-34), in an osteopenic rat model. Materials and Methods: Six-month-old female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human parathyroid hormone [hPTH(1-34); 40 μg/kg, 5 days/week], or vehicle for 60 days (days 60-120). Sham-operated and one group of OVX animals were injected with vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross-links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120 and analyzed by ELISA. At death, the right proximal tibial metaphysis was removed, and microcomputed tomography was performed for trabecular bone structure and processed for histomorphometry to assess bone cell activity. The left proximal tibia was used for nanoindentation/mechanical testing of individual trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as needed. Results: Ovariectomy at day 60 resulted in about a 50% loss of trabecular bone volume compared with sham-treated animals. By day 120 post-OVX, OVX + vehicle treated animals had decreased trabecular bone volume, connectivity, number, and high bone turnover compared with sham-operated animals [p < 0.05 from sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased trabecular thickness and bFGF increased trabecular number and connectivity. Histomorphometry revealed increased mineralizing surface and bone formation rate in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF-treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p < 0.05). Nanoindentation by atomic force microscope was performed on approximately 20 individual trabeculae per animal (three animals per group) and demonstrated that elastic modulus and hardness of the trabeculae in bFGF-treated animals were similar to that of the hPTH-treated and sham + vehicle-treated animals. Conclusion: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening existing trabeculae, whereas bFGF adds trabecular bone mass through increasing trabecular number and trabecular connectivity. These results suggest the possibility of sequential treatment paradigms for severe osteoporosis.

    Original languageEnglish (US)
    Pages (from-to)2105-2115
    Number of pages11
    JournalJournal of Bone and Mineral Research
    Volume18
    Issue number12
    DOIs
    StatePublished - Dec 2003

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    Teriparatide
    Anabolic Agents
    Bone and Bones
    Bone Remodeling
    Osteoporosis
    Cancellous Bone
    X-Ray Microtomography
    Biomedical Technology
    Elastic Modulus
    Osteocalcin
    Hardness
    Ovariectomy
    Tibia
    Osteogenesis
    Sprague Dawley Rats

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Both hPTH(1-34) and bFGF Increase Trabecular Bone Mass in Osteopenic Rats but They Have Different Effects on Trabecular Bone Architecture. / Lane, Nancy E; Yao, Wei; Kinney, John H.; Modin, Gunnard; Balooch, Mehdi; Wronski, Thomas J.

    In: Journal of Bone and Mineral Research, Vol. 18, No. 12, 12.2003, p. 2105-2115.

    Research output: Contribution to journalArticle

    @article{e0b5a05faa224dd5a4e4adb9e798227f,
    title = "Both hPTH(1-34) and bFGF Increase Trabecular Bone Mass in Osteopenic Rats but They Have Different Effects on Trabecular Bone Architecture",
    abstract = "Osteoporosis is a syndrome of excessive skeletal fragility that results from both the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF has been found to increase trabecular bone mass in osteoporotic rats. The purpose of this study was to compare how trabecular bone architecture, bone cell activity, and strength are altered by two different bone anabolic agents, bFGF and hPTH(1-34), in an osteopenic rat model. Materials and Methods: Six-month-old female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human parathyroid hormone [hPTH(1-34); 40 μg/kg, 5 days/week], or vehicle for 60 days (days 60-120). Sham-operated and one group of OVX animals were injected with vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross-links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120 and analyzed by ELISA. At death, the right proximal tibial metaphysis was removed, and microcomputed tomography was performed for trabecular bone structure and processed for histomorphometry to assess bone cell activity. The left proximal tibia was used for nanoindentation/mechanical testing of individual trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as needed. Results: Ovariectomy at day 60 resulted in about a 50{\%} loss of trabecular bone volume compared with sham-treated animals. By day 120 post-OVX, OVX + vehicle treated animals had decreased trabecular bone volume, connectivity, number, and high bone turnover compared with sham-operated animals [p < 0.05 from sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased trabecular thickness and bFGF increased trabecular number and connectivity. Histomorphometry revealed increased mineralizing surface and bone formation rate in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF-treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p < 0.05). Nanoindentation by atomic force microscope was performed on approximately 20 individual trabeculae per animal (three animals per group) and demonstrated that elastic modulus and hardness of the trabeculae in bFGF-treated animals were similar to that of the hPTH-treated and sham + vehicle-treated animals. Conclusion: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening existing trabeculae, whereas bFGF adds trabecular bone mass through increasing trabecular number and trabecular connectivity. These results suggest the possibility of sequential treatment paradigms for severe osteoporosis.",
    author = "Lane, {Nancy E} and Wei Yao and Kinney, {John H.} and Gunnard Modin and Mehdi Balooch and Wronski, {Thomas J.}",
    year = "2003",
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    language = "English (US)",
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    TY - JOUR

    T1 - Both hPTH(1-34) and bFGF Increase Trabecular Bone Mass in Osteopenic Rats but They Have Different Effects on Trabecular Bone Architecture

    AU - Lane, Nancy E

    AU - Yao, Wei

    AU - Kinney, John H.

    AU - Modin, Gunnard

    AU - Balooch, Mehdi

    AU - Wronski, Thomas J.

    PY - 2003/12

    Y1 - 2003/12

    N2 - Osteoporosis is a syndrome of excessive skeletal fragility that results from both the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF has been found to increase trabecular bone mass in osteoporotic rats. The purpose of this study was to compare how trabecular bone architecture, bone cell activity, and strength are altered by two different bone anabolic agents, bFGF and hPTH(1-34), in an osteopenic rat model. Materials and Methods: Six-month-old female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human parathyroid hormone [hPTH(1-34); 40 μg/kg, 5 days/week], or vehicle for 60 days (days 60-120). Sham-operated and one group of OVX animals were injected with vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross-links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120 and analyzed by ELISA. At death, the right proximal tibial metaphysis was removed, and microcomputed tomography was performed for trabecular bone structure and processed for histomorphometry to assess bone cell activity. The left proximal tibia was used for nanoindentation/mechanical testing of individual trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as needed. Results: Ovariectomy at day 60 resulted in about a 50% loss of trabecular bone volume compared with sham-treated animals. By day 120 post-OVX, OVX + vehicle treated animals had decreased trabecular bone volume, connectivity, number, and high bone turnover compared with sham-operated animals [p < 0.05 from sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased trabecular thickness and bFGF increased trabecular number and connectivity. Histomorphometry revealed increased mineralizing surface and bone formation rate in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF-treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p < 0.05). Nanoindentation by atomic force microscope was performed on approximately 20 individual trabeculae per animal (three animals per group) and demonstrated that elastic modulus and hardness of the trabeculae in bFGF-treated animals were similar to that of the hPTH-treated and sham + vehicle-treated animals. Conclusion: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening existing trabeculae, whereas bFGF adds trabecular bone mass through increasing trabecular number and trabecular connectivity. These results suggest the possibility of sequential treatment paradigms for severe osteoporosis.

    AB - Osteoporosis is a syndrome of excessive skeletal fragility that results from both the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF has been found to increase trabecular bone mass in osteoporotic rats. The purpose of this study was to compare how trabecular bone architecture, bone cell activity, and strength are altered by two different bone anabolic agents, bFGF and hPTH(1-34), in an osteopenic rat model. Materials and Methods: Six-month-old female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human parathyroid hormone [hPTH(1-34); 40 μg/kg, 5 days/week], or vehicle for 60 days (days 60-120). Sham-operated and one group of OVX animals were injected with vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross-links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120 and analyzed by ELISA. At death, the right proximal tibial metaphysis was removed, and microcomputed tomography was performed for trabecular bone structure and processed for histomorphometry to assess bone cell activity. The left proximal tibia was used for nanoindentation/mechanical testing of individual trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as needed. Results: Ovariectomy at day 60 resulted in about a 50% loss of trabecular bone volume compared with sham-treated animals. By day 120 post-OVX, OVX + vehicle treated animals had decreased trabecular bone volume, connectivity, number, and high bone turnover compared with sham-operated animals [p < 0.05 from sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased trabecular thickness and bFGF increased trabecular number and connectivity. Histomorphometry revealed increased mineralizing surface and bone formation rate in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF-treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p < 0.05). Nanoindentation by atomic force microscope was performed on approximately 20 individual trabeculae per animal (three animals per group) and demonstrated that elastic modulus and hardness of the trabeculae in bFGF-treated animals were similar to that of the hPTH-treated and sham + vehicle-treated animals. Conclusion: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening existing trabeculae, whereas bFGF adds trabecular bone mass through increasing trabecular number and trabecular connectivity. These results suggest the possibility of sequential treatment paradigms for severe osteoporosis.

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