Physiology of Bone Loss

Overview

Journal Radiol Clin North Am

Specialty Radiology

Date 2010 Jul 9

PMID 20609887

Citations 85

Authors

Bart L Clarke

Sundeep Khosla

Affiliations

Soon will be listed here.

Abstract

The physiology of bone loss in aging women and men is largely explained by the effects of gonadal sex steroid deficiency on the skeleton. In women, estrogen deficiency is the main cause of early rapid postmenopausal bone loss, whereas hyperparathyroidism and vitamin D deficiency are thought to explain age-related bone loss later in life. Surprisingly, estrogen deficiency also plays a dominant role in the physiology of bone loss in aging men. Many other factors contribute to bone loss in aging women and men, including defective bone formation by aging osteoblasts, impairment of the growth hormone/insulin-like growth factor axis, reduced peak bone mass, age-associated sarcopenia, leptin secreted by adipocytes, serotonin secreted by the intestine, and a long list of sporadic secondary causes. Further elucidation of the relative importance of each of these factors will lead to improved preventive and therapeutic approaches for osteoporosis.

Citing Articles

Serum A20 level is associated with bone mineral density in male patients with type 2 diabetes mellitus.

Han D, Liu J, Wang Y, Wang H, Yuan L, Jin W Front Endocrinol (Lausanne). 2025; 16:1490214.

PMID: 40078583 PMC: 11899168. DOI: 10.3389/fendo.2025.1490214.

[Basic Research on the Microstructure of Rat Bones in the High-Altitude Environment of Qinghai-Tibet Plateau].

Zhao S, Wang Z, Yin H, Wang C, Suo J, Liang B Sichuan Da Xue Xue Bao Yi Xue Ban. 2025; 55(6):1469-1476.

PMID: 39990840 PMC: 11839369. DOI: 10.12182/20241160505.

Dairy and Exercise for Bone Health: Evidence from Randomized Controlled Trials and Recommendations for Future Research.

Cheng N, Josse A Curr Osteoporos Rep. 2024; 22(6):502-514.

PMID: 39269594 DOI: 10.1007/s11914-024-00882-2.

Osteogenesis Study of Shell Nacre Cement with Older and Young Donor Bone Marrow Mesenchymal Stem/Stromal Cells.

Wilson B, Owston H, Iqbal N, Giannoudis P, McGonagle D, Pandit H Bioengineering (Basel). 2024; 11(2).

PMID: 38391629 PMC: 10886325. DOI: 10.3390/bioengineering11020143.

New Emerging Aspect of Herbal Extracts for the Treatment of Osteoporosis: Overview.

Kumari P, Shirumalla R, Bhalla V, Alam M Curr Rheumatol Rev. 2024; 20(4):361-372.

PMID: 38173067 DOI: 10.2174/0115733971273691231121131455.

References

Simonet W, Lacey D, Dunstan C, Kelley M, Chang M, Luthy R . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89(2):309-19. DOI: 10.1016/s0092-8674(00)80209-3. View

Boonen S, Mohan S, Dequeker J, Aerssens J, Vanderschueren D, Verbeke G . Down-regulation of the serum stimulatory components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, IGF binding protein [BP]-3, and IGFBP-5) in age-related (type II) femoral neck osteoporosis. J Bone Miner Res. 2000; 14(12):2150-8. DOI: 10.1359/jbmr.1999.14.12.2150. View

Gallagher J, Riggs B, DeLuca H . Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1980; 51(6):1359-64. DOI: 10.1210/jcem-51-6-1359. View

Yadav V, Oury F, Suda N, Liu Z, Gao X, Confavreux C . A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009; 138(5):976-89. PMC: 2768582. DOI: 10.1016/j.cell.2009.06.051. View

Bennett A, Wahner H, Riggs B, Hintz R . Insulin-like growth factors I and II: aging and bone density in women. J Clin Endocrinol Metab. 1984; 59(4):701-4. DOI: 10.1210/jcem-59-4-701. View

Girasole G, Jilka R, Passeri G, Boswell S, Boder G, Williams D . 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992; 89(3):883-91. PMC: 442934. DOI: 10.1172/JCI115668. View

Modder U, Achenbach S, Amin S, Riggs B, Melton 3rd L, Khosla S . Relation of serum serotonin levels to bone density and structural parameters in women. J Bone Miner Res. 2009; 25(2):415-22. PMC: 3153390. DOI: 10.1359/jbmr.090721. View

Khosla S . Update in male osteoporosis. J Clin Endocrinol Metab. 2010; 95(1):3-10. PMC: 2805483. DOI: 10.1210/jc.2009-1740. View

Srivastava S, Toraldo G, Weitzmann M, Cenci S, Ross F, Pacifici R . Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem. 2000; 276(12):8836-40. DOI: 10.1074/jbc.M010764200. View

10.

Charatcharoenwitthaya N, Khosla S, Atkinson E, McCready L, Riggs B . Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res. 2007; 22(5):724-9. DOI: 10.1359/jbmr.070207. View

11.

Oursler M, Cortese C, Keeting P, Anderson M, Bonde S, Riggs B . Modulation of transforming growth factor-beta production in normal human osteoblast-like cells by 17 beta-estradiol and parathyroid hormone. Endocrinology. 1991; 129(6):3313-20. DOI: 10.1210/endo-129-6-3313. View

12.

Genant H, Cann C, Ettinger B, GORDAN G . Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy. Ann Intern Med. 1982; 97(5):699-705. DOI: 10.7326/0003-4819-97-5-699. View

13.

Frost H . On our age-related bone loss: insights from a new paradigm. J Bone Miner Res. 1997; 12(10):1539-46. DOI: 10.1359/jbmr.1997.12.10.1539. View

14.

Kennel K, Riggs B, Achenbach S, Oberg A, Khosla S . Role of parathyroid hormone in mediating age-related changes in bone resorption in men. Osteoporos Int. 2003; 14(8):631-6. DOI: 10.1007/s00198-003-1417-0. View

15.

Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S . Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab. 2003; 88(11):5327-33. DOI: 10.1210/jc.2003-030736. View

16.

Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle W, Lacey D, Riggs B . Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003; 111(8):1221-30. PMC: 152939. DOI: 10.1172/JCI17215. View

17.

Khastgir G, Studd J, Holland N, Alaghband-Zadeh J, Fox S, Chow J . Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study. J Clin Endocrinol Metab. 2001; 86(1):289-95. DOI: 10.1210/jcem.86.1.7161. View

18.

Tobias J, Compston J . Does estrogen stimulate osteoblast function in postmenopausal women?. Bone. 1999; 24(2):121-4. DOI: 10.1016/s8756-3282(98)00156-2. View

19.

Marie P, Hott M, Launay J, Graulet A, Gueris J . In vitro production of cytokines by bone surface-derived osteoblastic cells in normal and osteoporotic postmenopausal women: relationship with cell proliferation. J Clin Endocrinol Metab. 1993; 77(3):824-30. DOI: 10.1210/jcem.77.3.8370705. View

20.

Gohel A, McCarthy M, Gronowicz G . Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. Endocrinology. 1999; 140(11):5339-47. DOI: 10.1210/endo.140.11.7135. View