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Inicio Endocrinología y Nutrición Agentes anabólicos óseos para el tratamiento de osteoporosis
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Vol. 51. Núm. 9.
Páginas 512-523 (Noviembre 2004)
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Vol. 51. Núm. 9.
Páginas 512-523 (Noviembre 2004)
Acceso a texto completo
Agentes anabólicos óseos para el tratamiento de osteoporosis
Bone Anabolic Agents For Osteoporosis Treatment
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9525
J.M. Quesada
Unidad de Metabolismo Mineral. Servicio de Endocrinología. Hospital Universitario Reina Sofía. Córdoba. España
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The concept of anabolic treatment in osteoporosis is entirely different from inhibition of bone resorption. Anabolic agents directly stimulate bone formation. Inherent in this concept is the potential for anabolic agents to increase bone mass to a far greater extent than antiresorptive drugs.

The present article reviews several anabolic therapies used in osteoporosis, including fluoride, growth hormone, insulin-like growth factor-I, parathyroid hormone, statins and strontium. Of these, parathyroid hormone (PTH) and strontium have emerged as the new paradigms in osteoporosis treatment. The Food and Drug Administration has authorized PTH for osteoporosis treatment, strontium therapy has recently been demonstrated to reduce fracture risk at spine and hip and the potential of statins in osteoporosis treatment is currently being evaluated.

Key words:
Osteoporosis
Fluoride
Growth hormone
Insulin-like growth factor-I
Parathyroid hormone
Strontiume
Statins

El concepto de tratamiento anabólico en osteoporosis es completamente diferente de la inhibición de la resorción ósea. Los agentes anabolizantes óseos estimulan directamente la formación ósea. Inherente a este concepto es el gran potencial de los fármacos anabólicos para aumentar la masa ósea y disminuir las fracturas osteoporóticas, mucho más que lo pueden hacer los fármacos antirresortivos.

Revisamos los agentes anabólicos evaluados previamente; el flúor, primer agente anabólico empleado en el tratamiento de la osteoporosis; la hormona de crecimiento y la somatomedina C o factor de crecimiento similar a la insulina tipo 1, con especial interés por los nuevos paradigmas emergentes en el tratamiento de la osteoporosis: la hormona paratiroidea, aprobada por la Food and Drug Administration para la indicación de osteoporosis; el estroncio, que recientemente ha demostrado su capacidad de reducir fracturas osteoporóticas, y las estatinas, cuyo potencial en la osteoporosis está en evaluación.

Palabras clave:
Osteoporosis
Flúor
Hormona de crecimiento
Somatomedina C
Hormona paratiroidea
Estroncio
Estatinas
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Biblografía
[1.]
NIH Consensus Statement.
Osteoporosis prevention, diagnosis, and therapy, 17 (2000), pp. 1-36
[2.]
Grupo de Trabajo de la Sociedad Española de Investigaciones Óseas y Metabolismo Mineral (SEIOMM).
Osteoporosis postmenopáusica. Guía de práctica clínica.
Rev Clin Esp, 203 (2003), pp. 496-506
[3.]
S.R. Cummings.
Melton LJ III. Epidemiology and outcomes of osteoporotic fractures.
Lancet, 359 (2002), pp. 1761-1767
[4.]
R.L. Jilka, R.S. Weinstein, T. Bellido, P. Roberson, A.M. Parfitt, S.C. Manolagas.
Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.
J Clin Invest, 104 (1999), pp. 439-446
[5.]
E. Seeman.
Osteoporosis. Pathogenesis of bone fragility in women and men.
Lancet, 359 (2002), pp. 1841-1850
[6.]
J.D. Currey.
The mechanical consequences of the variation in the mineral content of bone.
J Biomech, 2 (1969), pp. 1-11
[7.]
P.D. Delmas.
Treatment of postmenopausal osteoporosis.
Lancet, 359 (2002), pp. 2018-2026
[8.]
G.A. Rodan, T.J. Martin.
Therapeutic approaches to bone diseases.
Science, 289 (2002), pp. 1508-1514
[9.]
A.B. Hodsman, D.A. Hanley DA Watson, L.J. Fraher.
Parathyroid hormone.
Principles of bone biology, pp. 1305-1324
[10.]
J. Carverzasio, G. Palmer, J.P. Bonjour.
Fluoride mode of action.
Bone, 22 (1998), pp. 585-603
[11.]
B.L. Riggs, S.F. Hodgson, W.M. O'Fallon, E.Y. Chao, H.W. Wahner, J.M. Muhs, et al.
Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.
N Engl J Med, 322 (1990), pp. 802-809
[12.]
C.Y. Pak, J.E. Zerwekh, P.P. Antich, N.H. Bell, F.R. Singer.
Slow-release sodium fluoride in osteoporosis.
J Bone Miner Res, 11 (1996), pp. 561-564
[13.]
D.H. Gutteridge, G.O. Stewart, R.L. Prince, R.I. Price, R.W. Retallack, S.S. Dhaliwal, et al.
A randomised trial of sodium fluoride and estrogen in post menopausal osteoporotic vertebral fractures.
Osteoporosis Int, 13 (2002), pp. 158-170
[14.]
J.D. Ringe, L.C. Rovati.
Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates.
Calcif Tissue Int, 69 (2001), pp. 252-255
[15.]
J.Y. Reginster, L. Meurmans, B. Zegels, L.C. Rovati, H.W. Minne, G. Giacovelli, et al.
The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial.
Ann Intern Med, 129 (1998), pp. 1-8
[16.]
D. Haguenauer, V. Welch, B. Shea, P. Tugwell, G. Wells.
Fluoride for treating postmenopausal osteoporosis.
Cochrane Database Syst Rev, 4 (2000), pp. CD002825
[17.]
C.J. Rosen, J.P. Bilezikian.
Anabolic Therapy for osteoporosis.
J Clin Endocrinol Metab, 86 (2001), pp. 957-964
[18.]
D.C. Bauer, C.J. Rosen, J. Cauley, et al.
Low serum IGF-1 but not IGFBP-3 predicts hip and spine fracture: the study of osteoporotic fracture.
J Bone Miner Res, 23 (1998), pp. S561
[19.]
D. Rudman, A.G. Feller, H.S. Nagraj, G.A. Gergans, A.F. Lalitha PY Goldberg, et al.
Effects of human growth hormone in men over 60 years old.
N Engl J Med, 323 (1990), pp. 1-6
[20.]
L. Holloway, L. Kohlmeier, K. Kent, R. Marcus.
Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women.
J Clin Endocrinol Metab, 82 (1997), pp. 1111-1117
[21.]
E. Bauer, J. Aub, F. Albright.
Studies of calcium and phosphorus metabolism. A study of the bone trabeculae as a readily available reserve supply of calcium.
J Exp Med, 49 (1929), pp. 145-162
[22.]
M. Péhu, A. Policard, A. Dufort.
L'Ostéopétrose ou maladie des os marmoréens.
Presse Méd, 53 (1931), pp. 999-1003
[23.]
H. Selye.
On the stimulation of new bone formation with parathyroid extract and irradiated ergosterol.
Endocrinology, 16 (1932), pp. 547-558
[24.]
L.I. Pugsley, H. Selye.
The histological changes in the bone responsible for the action of parathyroid hormone on the calcium metabolism of the rat.
J Physiol, 79 (1933), pp. 113-117
[25.]
G.W. Tregear, J. Van Rietschoten, E. Greene, H.T. Keutmann, H.D. Niall, B. Reit, et al.
Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity.
Endocrinology, 93 (1974), pp. 1349-1353
[26.]
J. Reeve, R. Hesp, D. Williams, P. Hulme, L. Klenerman, S. Zanelli, et al.
Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis.
Lancet, 1 (1976), pp. 1035-1038
[27.]
J. Reeve, G.W. Tregear, J.A. Parsons.
Preliminary trial of low doses of human parathyroid hormone 1-34 peptide in treatment of osteoporosis.
Calcif Tissue, 21 (1976), pp. 469-477
[28.]
J. Reeve, P.J. Meunier, J.A. Parsons, M. Bernat, O.L.M. Bijvoet, P. Courpron, et al.
The anabolic effect of human parathyroid hormone fragment (hPTH 1-34) therapy on trabecular bone in involutional osteoporosis: report of a multi-centre trial.
Br Med J, 280 (1980), pp. 1340-1344
[29.]
L. Mosekilde, J. Reeve.
Treatment with PTH peptides.
Osteoporosis 2nd e.d. Vol. 2, pp. 725-746
[30.]
T.J. Gardella, H. Jüppner, F.R. Bringhurst, J.T. Potts Jr..
Receptors for parathyroid hormone (PTH) and PTH-related peptide.
Principles of bone biology, pp. 389-405
[31.]
J.S. Finkelstein.
Pharmacological mechanisms of therapeutics: parathyroid hormone.
Principles of bone biology, pp. 993-1005
[32.]
B.Y. Liu, J. Guo, B. Lanske, P. Divieti, H.M. Kronenberg, F.R. Bringhurst.
Conditionally immortalized murine bone marrow stromal cells mediate parathyroid hormone-dependent osteoclastogenesis in vitro.
Endocrinology, 139 (1998), pp. 1952-1964
[33.]
S. Khosla.
Minireview: the OPG/RANKL/RANK system.
Endocrinology, 142 (2001), pp. 5050-5055
[34.]
J.E. Aubin.
Heersche JNM. Cellular actions of parathyroid hormone on osteoblast and osteoclast differentiation.
The parathyroids, basic and clinical concepts, pp. 199-211
[35.]
R.L. Jilka, R.S. Weinstein, T. Bellido, P. Roberson, A.M. Parfitt, S.C. Manolagas.
Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone.
J Clin Invest, 104 (1999), pp. 439-446
[36.]
S.C. Manolagas.
Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.
Endocr Rev, 21 (2000), pp. 115-137
[37.]
E. Canalis, M. Centrella, W. Burch, T.L. McCarthy.
Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.
J Clin Invest, 83 (1989), pp. 60-65
[38.]
H. Dobnig, R.T. Turner.
Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells.
Endocrinology, 136 (1995), pp. 3632-3638
[39.]
C.P. Jerome, C.S. Johnson, H.T. Vafai, K.C. Kaplan, J. Bailey, B. Capwell, et al.
Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).
Bone, 25 (1999), pp. 301-309
[40.]
M. Kneissel, A. Boyde, J.A. Passer.
Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34).
Bone, 28 (2001), pp. 237-250
[41.]
M. Li, T.J. Wronski.
Response of femoral neck to estrogen depletion and parathyroid hormone in aged rats.
Bone, 16 (1995), pp. 551-557
[42.]
J.S. Thomsen, L.I. Mosekilde, J.A. Gasser.
Long-term therapy of ovariectomy-induced osteopenia with parathyroid hormone analog SDZ PTS 893 and bone maintenance in retired breeder rats.
Bone, 25 (1999), pp. 561-569
[43.]
M. Sato, G.Q. Zeng, C.H. Turner.
Biosynthetic human parathyroid hormone (1-34) effects on bone quality in aged ovariectomized rats.
Endocrinology, 138 (1997), pp. 4330-4337
[44.]
T. Hirano, D.B. Burr, C.H. Turner, M. Sato, L.C. Rick, H.M. Janet.
Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits.
J Bone Miner Res, 14 (1999), pp. 536-545
[45.]
C.S. Tam, J.N. Heersche, T.M. Murray, J.A. Parsons.
Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration.
Endocrinology, 10 (1982), pp. 506-512
[46.]
M.R. Rubin, J.P. Bilezikian.
New anabolic therapies in osteoporosis.
Endocrinol Metab Clin N Am, 32 (2003), pp. 285-307
[47.]
R.M. Neer, C.D. Arnaud, J.R. Zanchetta, R. Prince, G.A. Gaich, J.Y. Reginster, et al.
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
N Engl J Med, 344 (2001), pp. 434-441
[48.]
R. Marcus, O.H. Wang, J. Satterwhite, B. Mitlak.
The skeletal response to teriparatide is largely independent of age initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis.
J Bone Miner Res, 18 (2003), pp. 18-23
[49.]
F. Cosman, J. Nieves, L. Woelfert, C. Formica, S. Gordon, V. Shen, et al.
Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal.
J Bone Miner Res, 16 (2001), pp. 925-931
[50.]
M. Neer, D.M. Slovik, M. Daly, T. Potts, S.R. Nussbaum.
Treatment of postmenopausal osteoporosis with daily parathyroid hormone plus calcitriol.
Osteoporos Int, 1 (1993), pp. 204-205
[51.]
D.M. Slovik, D.I. Rosenthal, S.H. Doppelt, J.T. Potts Jr, M. Daly, J.A. Campbell, et al.
Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin.
J Bone Miner Res, 1 (1986), pp. 377-381
[52.]
A.B. Hodsman, L.J. Fraher, P.H. Watson, T. Ostbye, L.W. Stitt, J.D. Adachi, et al.
A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis.
J Clin Endocrinol Metab, 82 (1997), pp. 620-628
[53.]
J. Reeve, A. Mitchell, M. Tellez, P. Hulme, J.R. Green, B. Wardleys-Smith, et al.
Treatment with parathyroid peptides and estrogen replacement for severe post-menopausal vertebral osteoporosis: Long-term effects on spine and femur and determinants of magnitude of response.
J Bone Miner Metab, 19 (2001), pp. 102-114
[54.]
R. Lindsay, J. Nieves, C. Formica, E. Henneman, L. Woelfert, V. Shen, et al.
Randomised controlled study of effect of parathyroid hormone on vertebral bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis.
[55.]
J.S. Finkelstein, A. Klibanski, E.H. Schaefer, M.D. Hornstein, I. Schiff, R.M. Neer.
Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency.
N Engl J Med, 331 (1994), pp. 1618-1623
[56.]
S. Khosla.
Parathyroid hormone plus alendronate A combination that does not add u.p.
N Engl J Med, 349 (2003), pp. 1277-1279
[57.]
D.M. Black, S.L. Greenspan, K.E. Ensrud, L. Palermo, J.A. McGowan, T.F. Lang, et al.
The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis.
N Engl J Med, 349 (2003), pp. 1207-1215
[58.]
J.S. Finkelstein, A. Hayes, J.L. Hunzelman, J.J. Wyland, H. Lee, R.M. Neer.
Effects of parathyroid hormone, alendronate, or both in men with osteoporosis.
N Engl J Med, 349 (2003), pp. 1216-1226
[59.]
J.A. Gasser.
PTH and interactions with bisphosphonates.
J Musculoskel Neuron Interact, 1 (2000), pp. 53-56
[60.]
M. Li, L. Mosekilde, C.H. Sogaard, J.S. Thomsen, T.J. Wronski.
Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats.
Bone, 16 (1995), pp. 629-635
[61.]
P.D. Delmas, P. Vergnaud, M.E. Arlot, P. Pastoureau, P.J. Meunier.
Nilssen MHL. The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate. Is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system?.
Bone, 6 (1995), pp. 603-610
[62.]
S.L. Greenspan, R.D. Emkey.
Bone HG III. Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis: a randomized, double-blind, placebo-controlled trial.
Ann Intern Med, 137 (2002), pp. 875-883
[63.]
B. Ettinger, J. San Martin, G.G. Crans, I. Pavo.
Response of markers of bone turnover and bone density to teriparatide in postmenopausal women previously treated with an antiresorptive drug.
J Bone Miner Res, 18 (2003), pp. S15
[64.]
J.J. Body, G.A. Gaich, W.H. Scheele, P.M. Kulkarni, P.D. Millar, A. Peretz, et al.
A randomised double-blind trial to compare the efficacy of teriparatide (recombinant human parathyroid hormone 1-34) with alendronate in postmenopausal women with osteoporosis.
J Clin Endocrinol Metab, 87 (2002), pp. 4528-4535
[65.]
E.S. Kurland, F. Cosman, D.J. McMahon, C.J. Rosen, R. Lindsay, J.P. Bilezikian.
Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers.
J Clin Endocrinol Metab, 85 (2000), pp. 3069-3076
[66.]
E. Orwoll, W. Scheele, S. Paul, S. Adami, U. Syversen, A. Díez-Pérez, et al.
The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis.
J Bone Miner Res, 18 (2003), pp. 9-17
[67.]
N.E. Lane, S. Sánchez, G.W. Modin, H.K. Genant, E. Pierini, C.D. Arnaud.
Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis: results of a randomised controlled clinical trial.
J Clin Invest, 102 (1998), pp. 1627-1633
[68.]
E.F. Eriksen, R. Lindsay, W.H. Scheele, A.D. Clancy, B.H. Mitlak.
Incident vertebral fractures during an 18-month observation period following discontinuation of recombinant human parathyroid hormone (1-34) use in postmenopausal women with osteoporosis.
Osteoporos Int, 12 (2001), pp. S46
[69.]
J.R. Zanchetta, L. Rubio, A. Mango, C.E. Bogado.
Changes in BMD at different skeletal sites after discontinuation of treatment with rhPTH (1-34) in postmenopausal osteoporotic women.
J Bone Miner Res, 18 (2003), pp. S32
[70.]
R.S. Rittmaster, M. Bolognese, M.P. Ettinger, D.A. Hanley, A.B. Hodsman, D.L. Kendler, et al.
Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate.
J Clin Endocrinol Metab, 85 (2000), pp. 2129-2134
[71.]
E.K. Barbehenn, P. Lurie, S.M. Wolfe.
Osteosarcoma risk in rats using PTH 1-34.
Trends Endocrinol Metab, 12 (2001), pp. 383
[72.]
J.L. Vahle, M. Sato, G.G. Long, J.K. Young, P.C. Francis, J.A. Engelhardt, et al.
Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety.
Toxicol Pathol, 30 (2002), pp. 312-321
[73.]
J.r. Tashjian AH, B.A. Chabner.
Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women.
J Bone Miner Res, 17 (2002), pp. 1152-1161
[74.]
Endocrinologic and metabolic drugs advisory comité. Disponible en: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3761b2_fda.htm
[75.]
P.J. Marie, M. Hott, D. Modrowski, C. De Pollak, J. Guillemain, P. Deloffre, et al.
An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats.
J Bone Miner Res, 8 (1993), pp. 607-615
[76.]
P.J. Marie, P. Ammann, G. Boivin, C. Rey.
Mechanisms of action and therapeutic potential of strontium in bone.
Calcif Tissue Int, 69 (2001), pp. 121-129
[77.]
J.Y. Reginster, R. Deroisy, I. Jupsin.
Strontium ranelate: a new paradigm in the treatment of osteoporosis.
Drugs Today, 39 (2003), pp. 89-101
[78.]
J.Y. Reginster, P.J. Meunier.
Strontium ranelate phase 2 doseranging studies: PREVOS and STRATOS studies.
Osteoporos Int, 14 (2003), pp. 56-65
[79.]
P.J. Meunier, D.O. Slosman, P.D. Delmas, J.L. Sebert, M.L. Brandi, C. Albanese, et al.
Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis – A 2-year randomized placebo controlled trial.
J Clin Endocrinol Metab, 87 (2002), pp. 2060-2066
[80.]
J.Y. Reginster, R. Deroisy, M. Dougados, I. Jupsin, J. Colette, C. Roux.
Prevention of early postmenopausal bone loss by strontium ranelate: The randomized two year, double-masked, dose-ranging, placebo-controlled PREVOS trial.
Osteoporos Int, 13 (2002), pp. 925-931
[81.]
P.J. Meunier, J.Y. Reginster.
Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis.
Osteoporos Int, 14 (2003), pp. S66-76
[82.]
P.J. Meunier, C. Roux, E. Seeman, S. Ortolani, J.E. Badurski, T.D. Spector, et al.
The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.
N Engl J Med, 350 (2004), pp. 459-468
[83.]
J.Y. Reginster, A. Sawicki, J.P. Devogelaer, J.M. Padrino, J.M. Kauffman, D.V. Doyle, et al.
Strontium ranelate reduces the risk of hip fractures in women with postmenopausal osteoporosis.
Osteoporos Int, 13 (2002), pp. S14
[84.]
G. Mundy, R. Garrett, S. Harris, J. Chan, D. Chen, G. Rossini, et al.
Stimulation of bone formation in vitro and in rodents by statins.
Science, 286 (1999), pp. 1946-1949
[85.]
McFarlane SI, Muniyappa R, Francisco R, Sowers JR. Pleiotropic effects of statins: Lipid reduction and beyond. J Clin Endocrinol Metab 87:1451-8.
[86.]
D.C. Bauer.
HMG CoA reductase inhibitors and the skeleton: a comprehensive review.
Osteoporos Int, 14 (2003), pp. 273-282
[87.]
M. Sugiyama, T. Kodama, K. Konishi, K. Abe, S. Asami, S. Oikawa.
Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.
Biochem Biophys Res Commun, 271 (2000), pp. 688-692
[88.]
F.J. Maritz, M.M. Conradie, P.A. Hulley, R. Gopal, S. Hough.
Effect of statins on bone mineral density and bone histomorphometry in rodents.
Arterioscler Thromb Vasc Biol, 21 (2001), pp. 1636-1641
[89.]
L. Rejnmark, N.H. Buus, P. Verstergaard, L. Heickendorff, F. Andreasen, M.L. Larsen, et al.
Effects of simvastatin treatment in postmenopausal osteopenic women: a randomized controlled trial.
J Bone Miner Res, 18 (2003), pp. S32
[90.]
J.M. Quesada, J. Montero, R. Ruiz Roda, P. Ruiz, R. Cuenca, C. Aguilera, et al.
Efecto de la atorvastatina sobre la densidad ósea en mujeres postmenopáusicas hipercolesterolémicas.
REEMO, 12 (2003), pp. 25
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