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Calcified Tissue International
Published in: Calcified Tissue International 2/2008

01-02-2008

Alfacalcidol-Stimulated Focal Bone Formation on the Cancellous Surface and Increased Bone Formation on the Periosteal Surface of the Lumbar Vertebrae of Adult Female Rats

Authors: HaiYan Chen, XiaoYan Tian, XiaoQing Liu, Rebecca B. Setterberg, Mei Li, Webster S. S. Jee

Published in: Calcified Tissue International | Issue 2/2008

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Abstract

Purpose

To investigate the skeletal effects of alfacalcidol alone or in combination with exercise in intact adult female rats.

Methods

Seventy-four 8.5-month-old rats were orally administered 0, 0.005, 0.025, 0.05 or 0.1 μg/kg of alfacalcidol for 12 weeks, alone or in combination with exercise. Cancellous bone histomorphometric measurements were performed on the second lumbar vertebra.

Results

At 0.05 and 0.1 μg/kg, alfacalcidol caused a significant increase in cancellous bone volume, accompanied by an increase in trabecular architecture. Percent eroded surface, bone resorption and formation were suppressed by alfacalcidol treatment. However, mineral apposition rate was significantly increased, indicating osteoblast activity was increased. A positive balance between bone formation and resorption was observed in the rats treated with the highest dose of alfacalcidol. Alfacalcidol induced a unique bone formation site (“bouton”) on the cancellous surface. These boutons connected adjacent trabeculae and increased trabecular thickness. They exhibited both smooth and scalloped cement lines, suggesting that they were formed by minimodeling- and remodeling-based bone formation. Furthermore, alfacalcidol at 0.1 μg/kg increased periosteal bone formation of the lumbar transverse processes. Bipedal stance exercise alone did not have an effect on bone balance and bone turnover. There were no interactions between alfacalcidol and bipedal stance exercise except for a decrease in bone resorption.

Conclusion

Alfacalcidol exhibited both anti-catabolic and anabolic effects on bone in intact female rats. The effect of combined treatment with alfacalcidol and bipedal stance exercise was no better than that of alfacalcidol alone.
Literature
1.
Aloia JF, Vaswani A, Yeh JF (1988) Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 84:401–408PubMedCrossRef
2.
Reichel H, Koeffler HP, Hoeman AW (1989) The role of the vitamin D endocrine system in health and disease. N Engl J Med 320:980–991PubMedCrossRef
3.
Reid IR (1996) Vitamin D and its metabolites in the management of osteoporosis. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis. Academic Press, New York, pp 1169–1190
4.
Erben RG (2001) Vitamin D analogs and bone. J Musculoskelet Neuronal Interact 2:59–69PubMed
5.
Orimo H, Shiraki M, Hayashi T, Nakamura T (1987) Reduced occurrence of vertebral crush fracture in senile osteoporosis treated with 1α-hydroxyvitamin D3. Bone Miner 3:47–52PubMed
6.
Orimo H, Shiraki M, Hayashi T, Hoshino T, Onaya T, Miyazaki S, Kurosawa H, Nakamura T, Ogawa N (1994) Effects of 1α(OH)-vitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis. Calcif Tissue Int 54:370–373PubMedCrossRef
7.
Sairanen S, Karkkainen M, Tahtela R, Laitinen K, Makela P, Lamberg-Alardt C, Valimaki MJ (2000) Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (calcitriol) for four years. Calcif Tissue Int 267:122–127CrossRef
8.
Shiraki M, Ito H, Orimo H (1992) The ultra long-term treatment of senile osteoporosis with 1α-hydroxyvitamin D3. Bone Miner 20:223–234
9.
Ringe JD, Coster A, Meng T, Schacht E, Umback R (1999) Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium. Calcif Tissue Int 65:337–340PubMedCrossRef
10.
Okumura H, Yamamuro T, Kasai R, Hayashi T, Tada K, Nishii Y(1988). Effect of 1α-hydroxyvitamin D3 on osteoporosis induced by immobilization combined with ovariectomy in rats. Bone 8:351–355CrossRef
11.
Shiraishi A, Higashi S, Ohkawa H, Kubodera N, Hirasawa T, Ezawa I, Ikeda K, Ogata E (1999) The advantage of alfacalcidol over vitamin D in the treatment of osteoporosis. Calcif Tissue Int 65:311–316PubMedCrossRef
12.
Shiraishi A, Ohkawa H, Hayakawa N, Kubota N, Kubodera N, Ogata E (2006) Calcium supplementation does not reproduce the pharmacological efficacy of alfacalcidol for the treatment of osteoporosis in rats. Calcif Tissue Int 78:152–161PubMedCrossRef
13.
Shiraishi A, Higashi S, Masaki T, Ito M, Ikeda S, Nakamura T (2002) A comparison of alfacalcidol and menatetrenone for the treatment of bone loss in an ovariectomized rat model of osteoporosis. Calcif Tissue Int 71:69–79PubMedCrossRef
14.
Shiraishi A, Takeda S, Masaki T, Higuchi Y, Uchiyama Y, Kubodera N, Sato K, Ikeda K, Nakamuta T, Matsumoto T, Ogata E (2000) Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: Distinct actions from estrogen. J Bone Miner Res 15:770–779PubMedCrossRef
15.
Erben RG, Mosekilde L, Thomsen JS, Weber K, Stahr K, Leyshon A, Smith SY, Phipps R (2002) Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1α,25-dihydroxyvitamin D3. J Bone Miner Res 17:1498–1511PubMedCrossRef
16.
Erben RG, Bante U, Birner H, Stangassinger M (1997) 1α-hydroxyvitamin D2 partially dissociates between preservation of cancellous bone mass and effects on calcium homeostasis in ovariectomized rats. Calcif Tissue Int 60:449–456PubMedCrossRef
17.
Erben RG, Brown S, Stangassinger M (1998) Therapeutic efficacy of 1α,25-dihydroxyvitamin D3 and calcium in osteopenic ovariectomized rats: Evidence for a direct anabolic effect of 1α,25-hydroxyvitamin D3 on bone. Endocrinology 139:4319–4328PubMedCrossRef
18.
Erben RG, Bante U, Birner H, Stangassinger M (1997) Prophylactic effects of 1,24,25-dihydroxyvitamin D3 on ovariectomy-induced cancellous bone loss in the rat. Calcif Tissue Int 60:434–440PubMedCrossRef
19.
Erben RG, Weise H, Sinowatz F, Rambeck WA, Zucker H (1992) Vitamin D metabolites prevent vertebral osteopenia in ovariectomized rats. Calcif Tissue Int 50:228–236PubMedCrossRef
20.
Nishikawa T, Ogawa S, Kogita K, Manabe N, Katsumata T, Nakamura K, Kawaguchi H (2000) Additive effects of combined treatment with etidronate and alfacalcidol on bone mass and mechanical properties in ovariectomized rats. Bone 27:647–664PubMedCrossRef
21.
Li M, Li Y, Healy DR, Simmons HA, Ke HZ, Thompson DD (2003) Alfacalcidol restores cancellous bone in ovariectomized rats. J Musculoskelet Neuronal Interact 3:29–46
22.
Weber K, Golderg M, Stangassinger M, Erben RG (2001) 1α-hydroxyvitamin D2 is less toxic but not bone selective relative to 1α-hydroxyvitamin D3 in ovariectomized rats. J Bone Miner Res 16:639–651PubMedCrossRef
23.
Li M, Healy DR, Li Y, Simmons HA, Su M, Jee WSS, Shen VW, Thompson DD (2004) Alfacalcidol prevents age-related bone loss and causes an atypical pattern of bone formation in aged male rats. J Musculoskelet Neuronal Interact 4:22–32PubMed
24.
Radin EL, Paul IL, Rose RM (1972) Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet I:519–522CrossRef
25.
Aloia JF, Cohn SH, Ostuni JA, Cane R, Ellis K (1978) Prevention of involuntary bone loss by exercise. Ann Intern Med 89:365–358
26.
Simkin, Alyalon J, Leichter I (1987) Increased trabecular bone density due to bone-loading exercise in postmenopausal osteoporotic women. Calcif Tissue Int 40:59–67PubMedCrossRef
27.
Smith EL, Gilligan C, McAdam M, Ensign CP, Smith PE (1989) Deterring bone loss by exercise intervention in premenopausal and postmenopausal women. Calcif Tissue Int 44:312–321PubMedCrossRef
28.
Kirk S, Rude RK (1989) Effects of long-distance running on bone mass in women. J Bone Miner Res 4:59–63
29.
Peacock NA, Eisman JA, Yeatesm MG, Sambrook PN, Eberi S (1986) Physical fitness is a major determinant of femoral neck and lumbar spine bone mineral density. J Clin Invest 78:618–621
30.
Burr DB, Milgrom C, Boyd RD, Higgins WL, Robin G, Radin EL (1990) Experimental stress fracture of the tibia: Biological and mechanical etiology in rabbits. J Bone Joint Surg Br 72:370–375PubMed
31.
Yao W, Jee WSS, Frost HM (2000) Making rats rise to erect bipedal stance for feeding partially prevented orchidectomy-induced bone loss and added bone to intact rats. J Bone Miner Res 15:1158–1168PubMedCrossRef
32.
Yao W, Jee WSS, Chen J, Tam CS, Setterberg RB, Frost HM (2000) Erect bipedal stance exercise partially prevents orchidectomy-induced bone loss in the lumbar vertebrae. Bone 27:667–675PubMedCrossRef
33.
Yao W, Jee WSS, Frost HM (2001) A novel model to exercise rats: Making rats assume bipedal stance for feeding—raised cage model. J Musculoskelet Neuronal Interact 3:241–247
34.
Chen JL, Yao W, Frost HM, Li CY, Setterberg RB, Jee WSS (2001) Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats. Bone 2:126–133CrossRef
35.
Mo A, Yao W, Jee WSS (2002) Bipedal stance exercise and prostaglandin E2 (PGE2) and its synergistic effect in increasing bone mass and in lowering the PGE2 dose required to prevent ovariectomy-induced cancellous bone loss in aged rats. Bone 31:402–406PubMedCrossRef
36.
Li CY, Jee WSS, Chen JL, Mo A, Setterberg RB, Su M, Tian XY, Ling YF, Yao W (2003) Estrogen and “exercise” have a synthetic effect in preventing bone loss in the lumbar vertebrae and femoral neck of the ovariectomized rat. Calcif Tissue Int 72:42–49PubMedCrossRef
37.
Parfitt AM, Matthews CHE, Villanueva AR, Kleerekoper M, Frame B, Rao DS (1983) Relationships between surface, area, and thickness of iliac trabecular bone in aging and in osteoporosis. J Clin Invest 72:1396–1409PubMedCrossRef
38.
Parfitt AM, Drezner MK, Glorieux FH, Janis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: Standardization of nomenclature, symbols and units. Report to the ASBMR Histomorphometry Committee. J Bone Miner Res 2:595–610PubMedCrossRef
39.
Pataki A, Muller K, Green JR, Ma YF, Li QN, Jee WS (1997) Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: A comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec 249:458–468PubMedCrossRef
40.
Ke HZ, Li M, Jee WS (1992) Prostaglandin E2 prevents ovariectomy-induced cancellous bone loss in rats. Bone Miner 19:45–62PubMedCrossRef
41.
Hauge E, Mosekilde Le, Melsen F (1999) Missing observations in bone histomorphometry on osteoporosis: Implication and suggestions for an approach. Bone 25:389–395PubMedCrossRef
42.
Compston JE, Mellish RWE, Garrahan NJ (1987) Age-related changes in iliac crest trabecular microanatomic bone structure in man. Bone 8:289–292PubMedCrossRef
43.
Compston JE, Mellish RWE, Croucher P, Newcombe R (1989) Structural mechanisms of trabecular bone loss in man. Bone Miner 6:339–350PubMedCrossRef
44.
Tang L, Jee W, Ke HZ, Kimmel DB (1992) Restoring and maintaining bone in osteopenic female rat skeleton. I. Changes in bone mass and structure. J Bone Miner Res 7:1093–1104PubMed
45.
Takahashi HE, Hattner R, Epker B, Frost HM (1964) Evidence that bone resorption precedes formation at the cellular level. Henry Ford Hosp Med Bull 12:359–364
46.
Takahashi HE, Epker B, Frost HM (1964) Resorption proceeds formation activity. Surgical Forum 15:437–438PubMed
47.
Allen M, Follet H, Khurana M, Sato M, Burr D (2006) Anti-remodeling agents influence osteoblast activity differently in modeling- and remodeling-sites of canine rib. Calcif Tissue Int 79:255–261PubMedCrossRef
48.
Parfitt AM (2002) Recent contributions of iliac bone histomorphometry to understanding the anabolic effect of parathyroid hormone. IBMS BoneKEy, Jan 29. doi:10.​1138/​2002017
49.
Ma YL, Donley W, Eriksen EF (2003) Characteristics of modeling and remodeling osteons after teriparatide treatment. Bone 32:S225
50.
Kobayashi S, Takahashi HE, Ito A, Santo N, Nawata M, Horiuchi H, Ohta H, Ito A, Iorio R, Yamamoto N, Takaoka K (2003) Trabecular minimodeling in human iliac bone. Bone 32:163–169PubMedCrossRef
51.
Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: Early actions of Teriparatide. J Bone Miner Res 21:366–373PubMedCrossRef
52.
Frost HM (2004) The Utah paradigm of skeletal physiology, chapters 3 and 4. International Society of Musculoskeletal and Neuronal Interactions, Athens, Greece, 2004
53.
Erben EG (1996) Trabecular and endocortical bone surfaces in the rat: modeling and remodeling? Anat Rec 246:39–46
54.
Alhlborg H, Johnell O, Turner C, Rannevik G, Karlsson M (2003) Bone loss and bone size after menopause. N Engl J Med 349:327–334CrossRef
55.
Allen MR, Hock JM, Burr DB (2004) Periosteum: Biology, regulation, and response to osteoporosis therapies. Bone 35:1003–1012PubMedCrossRef
56.
Orwoll E (2003) Toward an expanded understanding of the role of the periosteum in skeletal health. J Bone Miner Res 18:949–954PubMedCrossRef
57.
Garn SM (1972) The course of bone gain and the phases of bone loss. Orthop Clin North Am 3:503–520PubMed
58.
Garn SM (1970) The earlier gain and later loss of cortical bone. Charles C Thomas, Springfield, IL
59.
Jee WSS (2000) Anabolic agents and osteoporosis: Quo vadis? J Musculoskelet Neuronal Interact 1:207–211
60.
Kalu ND, Banu J, Wang L (2000) How cancellous and cortical bones adapt to loading and growth hormone. J Musculoskelet Neuronal Interact 1:19–23PubMed
61.
Cui L, Ma YF, Yao W, Zhou H, Setterberg RB, Liang TC, Jee WSS (2001) Cancellous bone of aged rats maintains its capacity to respond vigorously to the anabolic effects of prostaglandin E2 by modeling-dependent bone gain. J Bone Miner Metab 19:29–37PubMedCrossRef
Metadata
Title
Alfacalcidol-Stimulated Focal Bone Formation on the Cancellous Surface and Increased Bone Formation on the Periosteal Surface of the Lumbar Vertebrae of Adult Female Rats
Authors
HaiYan Chen
XiaoYan Tian
XiaoQing Liu
Rebecca B. Setterberg
Mei Li
Webster S. S. Jee
Publication date
01-02-2008
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 2/2008
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-007-9086-1

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