Advertisement
Research Article| Volume 20, ISSUE 3, P623-638, September 2000

Anabolic Therapies

  • Robert Marcus
    Correspondence
    Address reprint requests to Robert Marcus, MD, Geriatrics Research, Education, and Clinical Center, VA Palo Alto Health Care System, GREEC 182-B, 3801 Miranda Avenue, Palo Alto, CA 94304.
    Affiliations
    From the Geriatrics Research, Education, and Clinical Center, VA Palo Alto Health Care System; and the Department of Medicine, Stanford University School of Medicine, Palo Alto, California
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      The possibility of anabolic therapy continues to excite the bone research community. Substantial clinical benefit may accrue with parathyroid hormone if preliminary evidence concerning antifracture efficacy is confirmed. Human growth hormone shows little or no promise as an anabolic agent for bone. Fluoride achieves substantial increases in bone mineral density, but its ability to prevent fractures remains highly contentious. It seems likely that, along with the possible addition of parathyroid hormone to the therapeutic armamentarium, preventive measures and potent antiresorptive drugs will remain the mainstay of osteoporosis therapy for the next several years.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Aloia J.F.
        • Vaswani A.
        • Kapoor A.
        • et al.
        Treatment of osteoporosis with calcitonin, with and without growth hormone.
        Metabolism. 1985; 34: 124-129
        • Aloia J.F.
        • Zanzi I.
        • Ellis K.
        • et al.
        Effects of growth hormone in osteoporosis.
        J Clin Endocrinol Metab. 1976; 43: 992-999
        • Baylink D.J.
        Fluoride therapy for osteoporosis.
        in: Marcus R. Feldman D. Kelsey J. Osteoporosis. Academic Press, San Diego1996: 1259-1278
        • Benz D.J.
        • Haussier M.R.
        • Thomas M.A.
        • et al.
        High-affinity androgen binding and androgenic regulation of alpha 1(1) procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells.
        Endocrinology. 1991; 128: 2723-2730
        • Boyce B.F.
        • Aufdemorte T.B.
        • Garrett I.R.
        • et al.
        Effects of interleukin-1 on bone turnover in normal mice.
        Endocrinology. 1989; 125: 1142-1150
        • Buchanan J.R.
        • Hospodar
        • Myers C.
        • et al.
        Effect of excess endogenous androgens on bone density in young women.
        J Clin Endocrinol Metab. 1988; 67: 937-943
        • Christiansen C.
        • Riis B.J.
        17β-estradiol and continuous norethisterone: A unique treatment for established osteoporosis in elderly women.
        J Clin Endocrinol Metab. 1990; 71: 836-841
        • Colvard D.
        • Eriksen E.
        • Keeting P.
        • et al.
        Evidence of steroid receptors in human osteoblast-like cells.
        Proc Natl Acad Sci U S A. 1989; 86: 854-857
        • Dempster D.W.
        Bone remodeling.
        in: Coe F.L. Favus M.J. Disorders of Bone & Mineral Metabolism. Raven Press, New York1992: 355-380
        • Feyen J.H.M.
        • Eiford P.
        • DiPadova F.E.
        • et al.
        Interleukin-6 is produced by bone and modulated by parathyroid hormone.
        J Bone Miner Res. 1989; 4: 633-638
        • Finkeistein J.S.
        • Klibanski A.
        • Arnold A.L.
        • et al.
        Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(l-34). A randomized controlled trial.
        JAMA. 1998; 280: 1067-1073
        • Finkeistein J.S.
        • Klibanski A.
        • Schaefer E.H.
        • et al.
        Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency.
        N Engl J Med. 1994; 331: 1618-1623
        • Fujita T.
        • Inoue T.
        • Morii H.M.
        • et al.
        Effect of an intermittent weekly dose of human parathyroid hormone (1-34) on osteoporosis: A randomized double masked prospective study using three dose levels.
        Osteoporos Int. 1999; 9: 296-306
        • Geusens P.
        • Dequeker J.
        Long-term effects of nandrolone decanoate, 1 alpha-hydroxy vitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: A double-blind controlled study.
        Bone. 1986; 1: 347-357
        • Guiness-Hey M.
        • Hock J.M.
        Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone.
        Metab Bone Dis Rel Res. 1984; 5: 177-182
        • Guiness-Hey M.
        • Hock J.M.
        Loss of the anabolic effect of parathyroid hormone on bone after discontinuation of hormone in rats.
        Bone. 1989; 10: 447-452
        • Harris W.H.
        • Heaney R.P.
        Effect of growth hormone on skeletal mass in adult dogs.
        Nature. 1969; 273: 403-404
        • Heaney R.P.
        Design considerations for clinical investigations of osteoporosis.
        in: Marcus R. Feldman D. Kelsey J. Osteoporosis. Academic Press, San Diego1996: 1137-1143
        • Hermann-Erlee M.P.M.
        • Heersche J.N.M.
        • Hekkelman J.W.
        • et al.
        Effects on bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1-34, 2-34, and 3-34.
        Endocr Res. 1976; 3: 21-22
        • Hesch R.-D.
        • Busch U.
        • Prokop M.
        • et al.
        Increase of vertebral density by combination therapy with pulsatile l-38hPTH and sequential addition of calcitonin nasal spray in osteoporotic patients.
        Calcif Tissue Int. 1989; 44: 176-180
        • Hesp R.
        • Hulme P.
        • Williams D.
        • et al.
        The relationship between changes in femoral bone density and calcium balance in patients with involutional osteoporosis treated with human parathyroid hormone fragment (hPTH 1-34).
        Metab Bone Dis Rel Res. 1981; 2: 331-334
        • Hickok L.R.
        • Toomey C.
        • Speroff L.
        A comparison of oesterified estrogens with and without methyltestosterone: Effects on endometrial histology and serum lipoproteins in postmenopausal women.
        Obstet Gynecol. 1993; 82: 919-924
        • Hock J.M.
        • Gera I.
        • Fonseca J.
        • et al.
        Human parathyroid hormone (1-34) increases bone mass in ovariectomized and orchidectomized rats.
        Endocrinology. 1988; 122: 2899-2904
        • Hodsman A.B.
        • Fraher L.J.
        • Watson P.H.
        • et al.
        A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclic parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis.
        J Clin Endocrinol Metab. 1997; 82: 620-628
        • Holloway L.
        • Butterfield G.
        • Hintz R.L.
        • et al.
        Effect of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women.
        J Clin Endocrinol Metab. 1994; 79: 470-479
        • Holloway L.
        • Kohlmeier L.
        • Kent K.
        • et al.
        Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women.
        J Clin Endocrinol Metab. 1997; 82: 1111-1117
        • Ishimi Y.
        • Miyaura C.
        • Jin C.H.
        • et al.
        IL-6 is produced by osteoblasts and induces bone resorption.
        J Immunol. 1990; 145: 3297-3303
        • Jilka R.L.
        • Weinstein R.S.
        • Bellido T.
        • et al.
        Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.
        J Clin Invest. 1999; 104: 439-446
        • Kalu D.N.
        • Pennock J.
        • Doyle F.H.
        • et al.
        Parathyroid hormone and experimental osteosclerosis.
        Lancet. 1970; 1: 1363-1366
        • Kleerekoper M.
        • Peterson E.L.
        • Nelson D.A.
        • et al.
        A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.
        Osteoporos Int. 1991; 1: 155-161
        • Lane N.E.
        • Sanchez S.
        • Modin G.W.
        • et al.
        Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis: Results of a randomized controlled clinical trial.
        J Clin Invest. 1998; 10: 1627-1633
        • Lindsay R.
        • Nieves J.
        • Formica C.
        • et al.
        Randomized controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis.
        Lancet. 1997; 350: 550-555
        • Liu C.C.
        • Kalu D.N.
        • Salerno E.
        • et al.
        Pre-existing bone loss associated with ovariectomy in rats is reversed by parathyroid hormone.
        J Bone Miner Res. 1991; 6: 1071-1080
        • Ljunghall S.
        • Johansson A.G.
        • Burman P.
        • et al.
        Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis.
        J Intern Med. 1992; 232: 59-64
        • Lowik C.W.G.M.
        • van der Pluijm G.
        • Bloys H.
        • et al.
        Parathyroid hormone and PTH-like protein stimulate interleukin-6 production by osteogenic cells: A possible role of interleukin-6 in osteoclastogenesis.
        Biochem Biophys Res Commun. 1989; 162: 1546-1552
        • MacDonald B.R.
        • Gallagher J.A.
        • Russell R.G.
        Parathyroid hormone stimulates the proliferation of cells derived from human bone.
        Endocrinology. 1986; 118: 2445-2449
        • Mann D.R.
        • Rudman C.G.
        • Akinbami M.A.
        • et al.
        Preservation of bone mass in hypogonadal female monkeys with recombinant human growth hormone administration.
        J Clin Endocrinol Metab. 1992; 74: 1263-1269
        • Marcus R.
        Normal and abnormal bone remodeling in man.
        Ann Rev Med. 1987; 38: 129-141
        • Meunier P.J.
        • Sebert J.L.
        • Reginster J.Y.
        • et al.
        Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis. The FAVO study.
        Osteoporos Int. 1998; 8: 4-12
        • Need G.A.
        • Horowitz M.
        • Bridges A.
        • et al.
        Effects of nandrolone decanoate and anti-resorptive therapy on vertebral density in osteoporotic women.
        Arch Intern Med. 1989; 149: 57-60
        • Nishida S.
        • Yamaguchi A.
        • Tanizawa T.
        • et al.
        Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow.
        Bone. 1994; 15: 717-723
        • Onishi T.
        • Zhang W.Y.
        • Cao X.
        • et al.
        The mitogenic effect of parathyroid hormone is associated with E2F-dependent activation of cyclin-dependent kinase 1 in osteoblast precursors.
        J Bone Miner Res. 1997; 12: 1596-1605
        • Orwoll E.
        • Klein R.
        Osteoporosis in men: Epidemiology, pathophysiology, and clinical characterization.
        in: Marcus R. Feldman D. Kelsey J. Osteoporosis. Academic Press, San Diego1996: 745-784
        • Pak C.Y.C.
        • Sakhaee K.
        • Piziak V.
        • et al.
        Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized clinical trial.
        Ann Intern Med. 1994; 120: 625-632
        • Papadakis M.A.
        • Grady D.
        • Black D.
        • et al.
        Growth hormone replacement in healthy older men improves body composition but not functional ability.
        Ann Intern Med. 1996; 124: 708-716
        • Parisien M.
        • Cosman F.
        • Mellish R.W.
        • et al.
        Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal women.
        J Bone Miner Res. 1995; 10: 1393-1399
        • Parsons J.A.
        • Reit B.
        Chronic response of dogs to parathyroid hormone infusion.
        Nature. 1974; 250: 254-257
        • Parsons J.A.
        • Robinson C.J.
        Calcium shift into bone causing transient hypocalcemia after injection of parathyroid hormone.
        Nature. 1971; 230: 581-582
        • Passeri M.
        • Pedrazzoni M.
        • Pioli G.
        • et al.
        Effects of nandrolone decanoate on bone mass in established osteoporosis.
        Maturitas. 1993; 17: 211-219
        • Reeve J.
        • Bradbeer J.N.
        • Arlot M.
        • et al.
        hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: Biochemical, kinetic and histological responses.
        Osteoporos Int. 1991; 1: 162-170
        • Reeve J.
        • Davies U.M.
        • Hesp R.
        • et al.
        Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.
        BMJ. 1990; 301: 314-318
        • Reeve J.
        • Meunier P.J.
        • Parsons J.A.
        • et al.
        Anabolic effect of human parathyroid hormone fragment (hPTH 1-34) therapy on trabecular bone in involutional osteoporosis: Report of a multi-centre trial.
        BMJ. 1980; 280: 1340-1344
        • Riggs B.L.
        • Hodgson S.
        • O’Fallon W.M.
        • et al.
        Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.
        N Engl J Med. 1990; 322: 802-809
        • Rudman D.
        • Feller A.G.
        • Nagraj H.S.
        • et al.
        Effects of human growth hormone in men over 60 years old.
        N Engl J Med. 1990; 323: 1-6
        • Selye H.
        On the stimulation of new bone formation with parathyroid extract and irradiated ergosterol.
        Endocrinology. 1932; 16: 547-558
        • Slovik D.M.
        • Rosenthal D.I.
        • Doppelt S.H.
        • et al.
        Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin D.
        J Bone Miner Res. 1986; 1: 377-381
        • Steinberg K.K.
        • Freni-Titulaer L.W.
        • DePeuy E.G.
        • et al.
        Sex steroids and bone density in premenopausal and postmenopausal women.
        J Clin Endocrinol Metab. 1989; 69: 533-539
        • Tam C.S.
        • Heersche J.N.M.
        • Murray T.M.
        • et al.
        Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: Differential effects of intermittent and continuous administration.
        Endocrinology. 1982; 110: 506-512
        • Tanaka S.
        • Haji M.
        • Nishi Y.
        • et al.
        Aromatase activity in human osteoblast-like cells.
        J Clin Endocrinol Metab. 1993; 52: 107-109
        • Walker D.G.
        The induction of osteopetrotic changes in hypophysectomized thyropara-thyroidectomized and intact rats of various ages.
        Endocrinology. 1971; 89: 1389-1406
        • Watts N.B.
        • Notelovitz M.
        • Timmons M.C.
        • et al.
        Comparison of oral estrogen and estrogens plus androgen on bone mineral density, menopausal symptoms and lipid-lipoprotein profiles in surgical menopause.
        Obstet Gynecol. 1995; 85: 529-537
        • West C.D.
        • Damast B.L.
        • Sarro S.D.
        • et al.
        Conversion of testosterone to estrogens in castrated, adrenalectomized human females.
        J Biol Chem. 1956; 218: 409-418
        • Wronski T.J.
        • Yen C.-F.
        Anabolic effects of parathyroid hormone in ovariectomized rats.
        Bone. 1994; 15: 51-58