Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone

Drugs and Aging

Volumn 12, Issue 2, 1998, Pages 149-168

  Coukell, Allan J ^a   Markham, Anthony ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; ANTINEOPLASTIC AGENT; CALCIUM ION; CLODRONIC ACID; ETIDRONIC ACID; HYDROXYAPATITE; MITHRAMYCIN; PAMIDRONIC ACID;

ALKALINE PHOSPHATASE BLOOD LEVEL; ANALGESIA; BONE MATRIX; BONE METASTASIS; BONE PAIN; BREAST CANCER; CALCIUM BLOOD LEVEL; CLINICAL TRIAL; DRUG INFUSION; DRUG MECHANISM; DRUG TOLERABILITY; DRUG UPTAKE; FEVER; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERCALCEMIA; HYPOCALCEMIA; INTRAVENOUS DRUG ADMINISTRATION; LYMPHOCYTOPENIA; MULTIPLE MYELOMA; MYALGIA; NEUTROPENIA; ORAL DRUG ADMINISTRATION; OSTEOCLAST; OSTEOLYSIS; PAGET BONE DISEASE; PATHOLOGIC FRACTURE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SCLERITIS; SURVIVAL; THROMBOPHLEBITIS; UVEITIS;

ANTINEOPLASTIC AGENTS; BONE NEOPLASMS; BONE RESORPTION; DIPHOSPHONATES; HUMANS; HYPERCALCEMIA; NEOPLASMS; OSTEITIS DEFORMANS; OSTEOLYSIS;

EID: 0031941807     PISSN: 1170229X     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002512-199812020-00007     Document Type: Review

References (112)

1. Reid IR, Wattie DJ, Evans MC, et al. Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. J Clin Endocrinol Metab 1994 Dec; 79: 1595-9
2. Orr-Walker B, Wattie DJ, Evans MC, et al. Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal osteoporosis. Clin Endocrinol 1997 Jan; 46: 87-92
3. Clarke NW, Holbrook IB, McClure J, et al. Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study. Br J Cancer 1991 Mar; 63: 420-3
4. Masud T, Slevin ML. Pamidronate to reduce bone pain in normocalcaemic patient with disseminated prostatic carcinoma [letter]. Lancet 1989 May 6; 1: 1021-2
5. Pelger RCM, Nijeholt A, Papapoulos SE. Short-term metabolic effecls of pamidronate in patients with prostatic carcinoma and bone metastases. Lancet 1989 Oct 7; 11: 865
6. Berruti A, Sperone P, Cerutti S, et al. Pamidronate administration to bone metastatic patients from prostate cancer (PC) improves bone metabolic derangement and bone pain [abstract no. 206]. Proc Am Soc Clin Oncol 1997; 16: 59a
7. Limouris GS, Manetou A, Moulopoulou A, et al. Evaluation of a combined radionuclide therapy for the treatment of mixed bony metastases [abstract no. 118] J Nucl Med 1996; 37 (5): 32P
8. Dodwell DJ. Malignant bone resorption: cellular and biochemical mechanisms. Ann Oncol 1992; 3: 257-67
9. Hosking DJ. Advances in the management of Paget's disease of bone. Drugs 1990 Dec; 40: 829-40
10. Averbuch SD. New bisphosphonates in the treatment of bone metastases. Cancer 1993; 72 Suppl.: 3443-52
11. Fitton A, McTavish D. Pamidronate: a review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs 1991 Feb; 41: 289-318
12. Body JJ, Coleman RE, Piccart M. Use of bisphosphonates in cancer patients. Cancer Treat Rev 1996 Jul; 22: 265-87
13. Boonekamp PM, van der Wee-Pals LJA, van Wijk-van Lennep MML, et al. Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1986; 1: 27-39
14. Evans CE, Braidman IP. Effects of two novel bisphosphonates on bone cells in vitro. Bone Miner 1994 Aug; 26: 45-107
15. Sahni M, Guenther HL, Fleisch H, et al. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 1993; 91: 2004-11
16. Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995 Oct; 10: 1478-87
17. Fenton AJ, Gutteridge DH, Kent GN, et al. Intravenous aminobisphosphonate on Paget's disease: clinical, biochemical, histomorphometric and radiological responses. Clin Endocrinol 1991; 34: 197-204
18. Adamson BB, Gallacher SJ, Byars J, et al. Mineralisation defects with pamidronate therapy for Paget's disease. Lancet 1993 Dec 11; 342: 1459-60
19. Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet 1994 Apr 16; 343: 953-4
20. van der Pluijm G, Vloedgraven H, van Beek F, et al. Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 1996 Aug 1; 98: 648-705
21. Coleman R, Vinholes J, Purohit O, et al. Effects of pamidronate on tumour marker levels in breast and prostate cancer correlation with clinical and biochemical response [abtract no. 1179]. Proc Am Soc Clin Oncol 1997; 16: 330a
22. Thürlimann B, Köberle D, Engler H, et al. Predictive factors for response to bisphosphonate treatment in malignant osteolytic bone disease: who will respond to pamidronate? [abstract no. 181]. Proc Am Soc Clin Oncol 1997; 16: 52a
23. Gallacher SJ, Fraser WD, Logue FC, et al. Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy. Calcif Tissue Int 1992 Dec; 51: 419-23
24. Body JJ, Dumon JC, Thirion M, et al. Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy. J Bone Miner Res 1993 Jun; 8: 701-6
25. Leyvraz S, Hess U, Flesch G, et al. Pharmacokinetics of pamidronate in patients with bone metastases. J Natl Cancer Inst 1992 May 20; 84: 788-92
26. Daley-Yates PT, Dodwell DJ, Pongchaidecha M, et al. The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases. Calcif Tissue Int 1991 Dec; 49: 433-5
27. Dodwell DJ, Howell A, Morton AR, et al. Infusion rate and pharmacokinetics of intravenous pamidronate in the treatment of tumour-induced hypercalcaemia. Postgrad Med J 1992 Jun; 68: 434-9
28. Redalieu F, Coleman JM, Chan K, et al. Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions. J Pharm Sci 1993 Jun; 82: 665-7
29. Berenson JR, Rosen L, Vescio R, et al. Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function. J Clin Pharmacol 1997; 37: 285-40
30. Glover D, Lipton A, Keller A, et al. Intravenous pamidronate disodium treatment of bone metastases in patients with breast cancer: a dose-seeking study. Cancer 1994 Dec 1; 74: 2949-55
31. Radziwill AJ, Thurlimann B, Jungi WF. Improvement of palliation in patients with osteolytic bone disease and unsatisfactory pain control after pretreatment with disodium pamidronate: an intra-patient dose escalation study. Onkologie 1993; 16 (3): 174-7
32. Purohit OP, Anthony C, Radstone CR, et al. High-dose intravenous pamidronate tor metastatic bone pain. Br J Cancer 1994 Sep; 70: 554-8
33. Thürlimann B, Morant R, Jungi WF, et al. Pamidronate for pain control in patients with malignant osteolytic bone disease: a prospective dose-effect study. Support Care Cancer 1994 Jan; 2:61-5
34. Coleman RE, Purohit OP, Vinholes J, et al. A randomised double-blind trial of pamidronate for metastatic bone pain [abstract]. Br J Cancer 1996 Mar; 73 Suppl. XXVI: 55
35. Koberle D, Thürlimann B, Engler H, et al. Double blind intravenous pamidronate (APD) 60 mg versus 90 mg in patients with malignant osteolytic bone disease and pain [abstract no. 182]. Proc Am Soc Clin Oncol 1997; 16: 53a
36. Conte PF, Latreille J, Mauriac L, et al. Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. J Clin Oncol 1996 Sep; 14: 2552-9
37. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 1996 Dec 12; 335: 1785-91
38. Lipton A, Theriault R, Leff R, et al. Reduction of skeletal related complications in breast cancer patients with osteolytic bone metastases receiving hormone therapy, by monthly pamidronate sodium (Aredia®) infusion [abstract]. Br J Cancer 1996 Jul; 74 Suppl. 28: 11
39. Hultborn R, Gundersen S, Rydén S, et al. Efficacy of pamidronate in breast cancer with bone metastases: a randomized double-blind placebo controlled multicenter study. Acta Oncol 1996; 35 Suppl. 5: 73-4
40. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Engl J Med 1996 Feb 22; 334: 488-93
41. Hortobagyi GN, Porter L, Theriault RL, et al. Long-term reduction of skeletal complications in breast cancer patients (pts) with osteolytic bone metastases receiving chemotherapy, by monthly 90 mg pamidronate (Aredia®) infusions [abstract no. 530]. Proc Am Soc Clin Oncol 1997; 16: 151a
42. Lipton A, Hershey PA, Theriault R, et al. Long-term reduction of skeletal complications in breast cancer patients (pts) with osteolytic bone metastases receiving hormone therapy, by monthly 90 mg pamidronate (Aredia®) infusions [abstract no. 531]. Proc Am Soc Clin Oncol 1997; 16: 152a
43. Lipton A. Bisphosphonates and breast carcinoma. Cancer 1997; 80 Suppl.: 1668-73
44. Lipton A, Theriault RL, Hortobagyi GN, et al. Long-term treatment with pamidronate reduces skeletal morbidity in women receiving endocrine treatment for advanced breast cancer and lytic bone lesions. Novartis Pharma AG (Basel), 1997 Oct 11: 1-26 (Data on file)
45. Hortobagyi GN, Theriault RL, Lipton A, et al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Novartis Pharma AG (Basel). 1997: 1-25 (Data on file)
46. Berenson JR. Bisphosphonates in multiple myeloma. Cancer 1997; 80 Suppl.: 1661-7
47. Berenson JR. The efficacy of pamidronate disodium in the treatment of osteolytic lesions and bone pain in multiple myeloma. Novartis Pharma AG (Basel), 1997: 1-32 (Data on file)
48. Ciba Aredia shows six-month difference in median time to first skeletal event in breast cancer patients; FDA Committee recommends breast cancer use. FDC Pink Sheet 1996 Jun 17; 58: 7-8
49. Aredia OK'd for bone metastases in US. Scrip 1996 Jun 21 (2139): 22
50. Mannix KA, Carmichael J, Harris AL, et al. Single high-dose (45 mg) infusions of aminohydroxypropylidene diphosphonate for severe malignant hypercalcemia. Cancer 1989 Sep 15; 64: 1358-61
51. Wimalawansa SJ. Significance of plasma PTH-rp in patients with hypercalcemia of malignancy treated with bisphosphonate. Cancer 1994 Apr 15; 73: 2223-30
52. Body JJ, Borkowski A, Cleeren A, et al. Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate. J Clin Oncol 1986 Aug; 4: 1177-83
53. Grutters JC, Hermus ARMM, de Mulder PHM, et al. Long-term follow up of breast cancer patients treated for hypercalcaemia with aminohydroxypropylidene bisphosphonate (APD). Breast Cancer Res Treat 1993; 25 (3): 277-81
54. Morton AR, Cantrill JA, Pillai GV, et al. Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma. BMJ 1988 Sep 24; 297: 772-3
55. Gucalp R, Ritch P, Wiernik PH, et al. Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia. J Clin Oncol 1992 Jan; 10: 132-42
56. Østenstad B, Andersen OK. Disodium pamidronate versus mithramycin in the management of tumour-associated hypercalcemia. Acta Oncol 1992; 31: 861-4
57. Purohit OP, Radstone CR, Anthony C. A randomised double-blind comparison of intravenous pamidronate and clodronate in the hypercalcaemia of malignancy. Br J Cancer 1995 Nov; 72: 1289-93
58. Thürlimann B, Waldburger R, Senn HJ, et al. Plicamycin and pamidronate in symptomatic tumor-related hypercalcemia: a prospective randomized crossover trial. Ann Oncol 1992 Aug; 3: 619-23
59. Vinholes J, Guo C-Y, Purohit OP, et al. Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malicnancy. J Clin Oncol 1997 Jan; 15: 131-8
60. Neskovi-Konstantinovi Z, Mitrovi L, Petrovi J, et al. Treatment of tumour-induced hypercalcaemia in advanced breast cancer patients with three different doses of disodium pamidronate adapted to the initial level of calcaemia. Support Care Cancer 1995 Nov; 3: 422-4
61. Morton AR, Cantrill JA, Craig AE, et al. Single dose versus daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy. Br Med J Clin Res Ed 1988 Mar 19; 296: 811-4
62. Gallacher SJ, Ralston SH, Fraser WD, et al. A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia. Bone Miner 1991 Dec; 15: 249-56
63. Nussbaum SR, Younger J, VandePol CJ, et al. Single-dose intravenous therapy with pamidronate for the treatment ot hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages. Am J Med 1993 Sep; 95: 297-304
64. Body JJ, Dumon JC. Treatment of tumour-induced hypercalcaemia with the bisphosphonate pamidronate: dose-response relationship and influence of tumour type. Ann Oncol 1994 Apr; 5: 359-63
65. Walls J, Ratcliffe WA, Howell A, et al. Response to intravenous bisphosphonate therapy in hypercalcaemic patients with and without bone metastases: the role of parathyroid hormone-related protein. Br J Cancer 1994 Jul; 70: 169-72
66. Pecherstorfer M, Thiébaud D. Treatment of resistant tumor-induced hypercalcemia with escalating doses of pamidronate. Ann Oncol 1992 Aug; 3: 661-3
67. Wimalawansa SJ. Optimal frequency of administration of pamidronate in patients with hypercalcaemia of malignancy. Clin Endocrinol 1994 Nov; 41: 591-5
68. Ralston SH, Gallacher SJ, Patel U, et al. Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia. Lancet 1989; II: 1180-2
69. Kanis JA, McCloskey EV, Paterson AHG. Use of diphosphonates in hypercalcaemia due Io malignancy [letter]. Lancet 1990; 335: 170-1
70. Ralston SH, Gardner MD, Dryburgh FJ, et al. Comparison of aminohydroxypropylidene diphosphonate, mithramycin, and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia. Lancet 1985 Oct 26; II: 907-10
71. Delmas PD, Meunier PJ. The management of Paget's disease of bone. N Engl J Med 1997 Feb 20; 336: 558-66
72. Meunier PJ, Vignot E. Therapeutic strategy in Paget's disease of bone. Bone 1995 Nov; 17 (5 Suppl): 489S-91S
73. Fraser TRC, Ibbertson HK, Holdaway IM, et al. Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate): a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate). Aust N Z J Med 1984; 14: 811-8
74. Gutteridge DH, Retallack RW, Ward LC, et al. Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: a 2-year study. Bone 1996; 19 (4): 387-94
75. Bombassei GJ, Yocono M, Raisz LG. Effects of intravenous pamidronate therapy on Paget's disease of bone. Am J Med Sci 1994 Oct; 308: 226-33
76. Cantrill JA, Buckler HM, Anderson DC. Low dose intravenous 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) for the treatment of Paget's disease of the bone. Ann Rheum Dis 1986; 45: 1012-8
77. Chakravarty K, Merry P, Scott DGI. A single infusion of bisphosphonate AHPrBP in the treatment of Paget's disease of bone. J Rheumatol 1994 Nov; 21: 2118-21
78. Gallacher SJ, Boyce BF, Patel U, et al. Clinical experience with pamidronate in the treatment of Paget's disease of bone. Ann Rheum Dis 1991 Dec; 50: 930-3
79. Harinck HI, Papapoulos SE, Blanksma HJ, et al. Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). Br Med J Clin Res Ed 1987 Nov 21; 295: 1301-5
80. Patel S, Stone MD, Coupland C, et al. Determinants of remission of Paget's disease of bone. J Bone Miner Res 1993 Dec; 8: 1467-73
81. Pepersack T, Karmali R, Gillet C, et al. Paget's disease of bone: five regimens of pamidronate treatment. Clin Rheumatol 1994 Mar; 13: 39-44
82. Ryan PJ, Sherry M, Gibson T, et al. Treatment of Paget's disease by weekly infusions of 3-aminohydroxypropylidene-1,1-bisphosphonate (APD). Br J Rheumatol 1992 Feb; 31: 97-101
83. Thiébaud D, Jaeger P, Gobelet C, et al. A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget's disease of bone. Am J Med 1988; 85: 207-12
84. Thiebaud D, Portmann L, Burckhardt P, Moderate Paget's disease treated with pamidronate: comparison of various infusion rates for a 60-mg single dose. Semin Arthritis Rheum 1994 Feb; 23: 279
85. Watts RA, Skingle SJ, Bhambhani MM, et al. Treatment of Paget's disease of bone with single dose intravenous pamidronate. Ann Rheum Dis 1993 Aug; 52: 616-8
86. Wimalawansa SJ, Gunasekera RD. Pamidronate is effective for Paget's disease of bone refractory to conventional therapy. Calcif Tissue Int 1993 Oct; 53: 237-41
87. Stone MD, Hawthorne AB, Kerr D, et al. Treatment of Paget's disease with intermittent low-dose infusions of disodium pamidronate. J Bone Miner Res 1990 Dec; 5: 1231-5
88. Ismail AA, Fox P, Stamp TCB, et al. Treatment of Paget's disease of bone with intravenous pamidronate: comparison of 2 different modes of treatment [letter]. J Rheumatol 1997; 24 (11): 2266-7
89. Ismail AA, Fox P, Godlstein AJ, et al. Treatment of Pagets disease with I-V pamidronate (APD) - four year follow up [abstract]. Br J Rheumatol 1994; 33 Suppl. 2: 33
90. Le Goff P, Saraux A, Valls-Bellec I, et al. Treatment of Paget's disease with pamidronate: usefulness of repeated infusions [abstract no. J91]. Rev Rhum English Ed 1996; 63: 760
91. Yap AS, Mortimer RH, Jacobi JM, et al. Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin. Horm Res 1991; 36 (1-2): 70-4
92. Cundy T, Wattie D, King AR. High-dose pamidronate in the management of resistant Paget's disease. Calcif Tissue Int 1996 Jan; 58: 6-8
93. Ryan PJ, Gibson T, Fogelman I. Bone scintigraphy following intravenous pamidronate for Paget's disease of bone. J Nucl Med 1992 Sep; 33: 1584-93
94. Johansen A, Stone M, Rawlinson F. Bisphosphonates and the treatment of bone disease in the elderly. Drugs Aging 1996 Feb; 8: 113-26
95. Buckler HM, Mercer SJ, Davison CE, et al. Does an initial test dose of pamidronate minimise transient side effects in Paget's disease of bone? [abstract]. Bone 1995 Jan; 16 Suppl.: 212S
96. Mautalen CA, Casco CA, Gonzalez D, et al. Side effects of disodium aminohydroxypropylidene diphosphonate (APD) during treatment of bone diseases. BMJ 1984; 288: 828-9
97. Macarol V, Fraunfelder FT. Pamidronate disodium and possible ocular adverse drug reactions. Am J Ophthalmol 1994 Aug 15; 118: 220-4
98. Des Grottes JM, Schrooyen M, Dumon JC, et al. Retrobulbar optic neuritis after pamidronate administration in a patient with a history of cutaneous porphyria. Clin Rheumatol 1997 Jan; 16: 93-5
99. Stewart GO, Stuckey BGA, Ward LC, et al. Iritis following intravenous pamidronate. Aust N Z J Med 1996 Jun; 26: 414-5
100. Machado CK, Flombaum CD. Safety of pamidronate in patients with renal failure and hypercalcemia. Clin Nephrol 1996 Mar; 45: 175-9
101. Watters J, Gerrard G, Dodwell D. The management of malignant hypercalcaemia. Drugs 1996 Dec; 52: 837-48
102. Ciba-Geigy Corporation. Aredia®: pamidronate disodium for injection [prescribing information]. Summit (NJ), USA: Ciba-Geigy Corporation; 1996, C96-51 (rev. 8/96)
103. Disodium pamidronate. British national formulary. 34th ed. London: British Medical Association, 1997 Sep: 331
104. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997 Jan; 69: 1-18
105. Houston SJ, Rubens RD. The systemic treatment of bone metastases. Clin Orthop Relat Res 1995; 312: 95-104
106. Kanis JA. Bone and cancer: pathophysiology and treatment of metastases. Bone 1995 Aug; 17 Suppl.: 101-5
107. Belch AR, Bergsagel DE, Wilson K, et al. Effect of daily etidronate on the osteolysis of multiple myeloma. J Clin Oncol 1991; 9: 1397-402
108. Lahtinen R, Laakso M, Palva I, et al. Randomised, placebo-controlled, multicentre trial of clodronate in multiple myeloma. Lancet 1992; 340: 1049-52
109. Paterson AHG, Powles TJ, Kanis JA, et al. Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 1993; 11: 59-65
110. Kovacs CS, MacDonald SM, Chik CL, et al. Hypercalcemia of malignancy in the palliative care patient: a treatment strategy. J Pain Symptom Manage 1995 Apr; 10: 224-32
111. Bilezikian JP. Management of acute hypercalcemia. N Engl J Med 1992 Apr 30; 326: 1196-203
112. Clissold SP, Fitton A, Chrisp P. Intranasal salmon calcitonin: a review of its pharmacological properties and potential utility in metabolic bone disorders associated with aging. Drugs Aging 1991 Sep-Oct; 1: 405-23