3 Osteopenia (Low Bone Mass)

Suggested citation: Endocrine Society. Endocrine Facts and Figures: Bone and Mineral. First Edition. 2016.

Low bone mass, also termed, osteopenia, is defined as bone density in which the T-score is between 1.0 and 2.49 [standard deviations below average (-1.0 to -2.49)] in postmenopausal women and men age >50 years.61

3.1 PREVALENCE AND INCIDENCE

The prevalence of osteopenia is higher in women than men (Table 14).3 Several conditions have been associated with the greater likelihood of reduced bone mass. A European study has linked metabolic syndrome with a higher prevalence of low bone mass in middle-aged men.62 Long-term antiepileptic drug use has also been associated with both osteopenia and osteoporosis.63

Table 14. Prevalence of osteopenia in United States adults, 1997.
Data Source Population Prevalence
Men Women
NHANES, Centers for Disease Control and Prevention 2005-2006 Nationally representative sample of US population age ≥ 50 years 28-47% 30-50%
Abbreviations: NAHNES, National Health and Nutrition Examination Survey
Note: NHANES III aimed to provide reliable estimates for three racial/ethnic groups: non-Hispanic Caucasians, non-Hispanic African Americans, and Mexican Americans. Number eligible to participate = 10,995; number interviewed = 8,654 (74%); number examined = 7,155 (65%).

Source: Looker et al. 19973

3.2 DEMOGRAPHIC DIFFERENCES

In 2010, researchers compared the prevalence of osteopenia in the femur neck and total hip in US men and women 50 years of age or older in terms of sex and race; in addition, they compared data from NHANES III and NHANES 2005–2006 (Table 15).64 With the exception of osteopenia in the total hip among Mexican American women, the prevalence between the two datasets did not differ significantly.

Table 15. Osteopenia in the femur neck and total hip in United States men and women age 50 years and older of different races: comparison of data from NHANES III (n = 6,401) and NHANES 2005–2006 (n = 1,601)
Femur Neck Total Hip
NHANES III NHANES
2005–2006
NHANES III NHANES
2005–2006
Women Non-Hispanic Caucasian 51% 52% 41% 39%
Non-Hispanic African American 36% 36% 28% 25%
Mexican American 47% 38% 38% 22% *
Total 49% 50% 39% 37%
Men Non-Hispanic Caucasian 25% 33% 18% 14%
Non-Hispanic African American 20% 22% 12% 7%
Mexican American 27% 34% 13% 12%
Total 34% 32% 17% 13%
Note: *, p < 0.05 between NHANES III and NHANES 2005-2006 within sex and race with Bonferroni adjustment.

Source: Looker et al. 201064

3.3 LIFE EXPECTANCY AND MORTALITY

An Australian study reported that among patients aged 60 years or older, those with osteopenia (with or without osteoporosis) experienced a greater burden of fractures and associated mortality.65

3.4 KEY TRENDS AND HEALTH OUTCOMES

It is important to distinguish between patients with osteopenia who require treatment and those who do not, since osteopenia is not a disease but a condition that may or may not be associated with increased fracture risk. To this end, it is recommended that clinicians assess risk in patients with DXA-defined osteopenia using a risk calculator such as the FRAX, developed by the WHO’s Collaborating Centre for Metabolic Bone Diseases at Sheffield University, rather than by exclusively using T-scores.66,67 Many individuals who should be treated are not being treated, despite the availability of a number of effective pharmacologic agents.68 Data from FRAX and DXA analyses may be effective in suggesting appropriate therapies for those who meet guidelines.66

References

  1. World Health Organization. Assessment of Fractue Risk and Its Application to Screening for Postmenopausal Osteoporosis. Geneva, Switzerland: World Health Organization; 1994.
  2. Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, Kleerekoper M, Luckey MM, McClung MR, Pillack RP, Petak SM, AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2010;16 Suppl 3:1-37.
  3. Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older U.S. adults from NHANES III. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1997;12(11):1761-1768.
  4. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2007;22(3):465-475.
  5. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics–2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115(5):e69-171.
  6. Society AC. Cancer Facts and Figures, 2006. Atlanta, GA: American Cancer Society; 2006.
  7. World Health Organization. Assessment of osteoporosis at the primary health care level. Summary Report of a WHO Scientific Group. 2007; WHO, Geneva. www.who.int/chp/topics/rheumatic/en/index.html. Accessed August 31, 2015.
  8. Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nature reviews. Rheumatology. 2009;5(12):667-676.
  9. Compton JT, Lee FY. A review of osteocyte function and the emerging importance of sclerostin. The Journal of bone and joint surgery. American volume. 2014;96(19):1659-1668.
  10. Bone HG, Dempster DW, Eisman JA, Greenspan SL, McClung MR, Nakamura T, Papapoulos S, Shih WJ, Rybak-Feiglin A, Santora AC, Verbruggen N, Leung AT, Lombardi A. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture Trial. Osteoporosis International. 2015;26(2):699-712.
  11. Costa AG, Cusano NE, Silva BC, Cremers S, Bilezikian JP. Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis. Nature reviews. Rheumatology. 2011;7(8):447-456.
  12. Leder BZ, O’Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. The journal of clinical endocrinology and metabolism. 2014;100(2):697-706.
  13. Karsenty G, Oury F. Regulation of male fertility by the bone-derived hormone osteocalcin. Molecular and cellular endocrinology. 2014;382(1):521-526.
  14. Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. The Journal of clinical investigation. 2014;124(4):1-13.
  15. Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, Srinivas P, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. The Journal of clinical investigation. 2013;123(6):2421-2433.
  16. Kajimura D, Lee HW, Riley KJ, Arteaga-Solis E, Ferron M, Zhou B, Clarke CJ, Hannun YA, DePinho RA, Guo XE, Mann JJ, Karsenty G. Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1. Cell metabolism. 2013;17(6):901-915.
  17. Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature. 2012;481(7381):314-320.
  18. Sims NA, Vrahnas C. Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts. Archives of biochemistry and biophysics. 2014;561:22-28.
  19. Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell … and more. Endocrine reviews. 2013;34(5):658-690.
  20. Henriksen K, Karsdal MA, Martin TJ. Osteoclast-derived coupling factors in bone remodeling. Calcified tissue international. 2014;94(1):88-97.
  21. Sims NA, Walsh NC. Intercellular cross-talk among bone cells: new factors and pathways. Current osteoporosis reports. 2012;10(2):109-117.
  22. Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Current osteoporosis reports. 2013;11(2):147-155.
  23. Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, McCloskey EV, Kanis JA, Bilezikian JP. Trabecular bone score: a noninvasive analytical method based upon the DXA image. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(3):518-530.
  24. Sandino C, Kroliczek P, McErlain DD, Boyd SK. Predicting the permeability of trabecular bone by micro-computed tomography and finite element modeling. Journal of biomechanics. 2014;47(12):3129-3134.
  25. Farr JN, Drake MT, Amin S, Melton LJ, 3rd, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(4):787-795.
  26. Randall C, Bridges D, Guerri R, Nogues X, Puig L, Torres E, Mellibovsky L, Hoffseth K, Stalbaum T, Srikanth A, Weaver JC, Rosen S, Barnard H, Brimer D, Proctor A, Candy J, Saldana C, Chandrasekar S, Lescun T, Nielson CM, Orwoll E, Herthel D, Kopeikin H, Yang HT, Farr JN, McCready L, Khosla S, Diez-Perez A, Hansma PK. Applications of a New Handheld Reference Point Indentation Instrument Measuring Bone Material Strength. Journal of medical devices. 2013;7(4):410051-410056.
  27. Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. The Cochrane database of systematic reviews. 2011(7):Cd000333.
  28. Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. The Cochrane database of systematic reviews. 2014;4:Cd000227.
  29. Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(11):2520-2526.
  30. Sanders S, Geraci SA. Osteoporosis in postmenopausal women: considerations in prevention and treatment: (women’s health series). Southern medical journal. 2013;106(12):698-706.
  31. Foundation NO. America’s Bone Health: The State of Osteoporosis and low bone mass in our nation. Washington, DC: The Foundation; 2002.
  32. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761-1767.
  33. Melton LJ, 3rd, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL. Prevalence and incidence of vertebral deformities. Osteoporosis International. 1993;3(3):113-119.
  34. Clarke BL, Khosla S. Assessing the true impact of recurrent fractures on fracture risk. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2009;24(9):1512-1514.
  35. Orwig DL, Chan J, Magaziner J. Hip fracture and its consequences: differences between men and women. The orthopedic clinics of north america. 2006;37(4):611-622.
  36. Forsen L, Sogaard AJ, Meyer HE, Edna T, Kopjar B. Survival after hip fracture: short- and long-term excess mortality according to age and gender. Osteoporosis International. 1999;10(1):73-78.
  37. Lee YK, Jang S, Jang S, Lee HJ, Park C, Ha YC, Kim DY. Mortality after vertebral fracture in Korea: analysis of the National Claim Registry. Osteoporosis International. 2012;23(7):1859-1865.
  38. Chaysri R, Leerapun T, Klunklin K, Chiewchantanakit S, Luevitoonvechkij S, Rojanasthien S. Factors related to mortality after osteoporotic hip fracture treatment at Chiang Mai University Hospital, Thailand, during 2006 and 2007. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2015;98(1):59-64.
  39. Vaseenon T, Luevitoonvechkij S, Wongtriratanachai P, Rojanasthien S. Long-term mortality after osteoporotic hip fracture in Chiang Mai, Thailand. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2010;13(1):63-67.
  40. Cauley JA. Defining ethnic and racial differences in osteoporosis and fragility fractures. Clinical orthopaedics and related research. 2011;469(7):1891-1899.
  41. Morin S, Lix LM, Azimaee M, Metge C, Caetano P, Leslie WD. Mortality rates after incident non-traumatic fractures in older men and women. Osteoporos Int. 2011;22(9):2439-2448.
  42. Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L, Kennedy CC, Prior JC, Olszynski WP, Davison KS, Goltzman D, Thabane L, Gafni A, Papadimitropoulos EA, Brown JP, Josse RG, Hanley DA, Adachi JD. Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2009;181(5):265-271.
  43. Svejme O, Ahlborg HG, Nilsson JA, Karlsson MK. Early menopause and risk of osteoporosis, fracture and mortality: a 34-year prospective observational study in 390 women. BJOG : an international journal of obstetrics and gynaecology. 2012;119(7):810-816.
  44. Licata AA. Diagnosing primary osteoporosis: it’s more than a T score. Cleveland Clinic journal of medicine. 2006;73(5):473-476.
  45. Binkley N, Adler R, Bilezikian JP. Osteoporosis diagnosis in men: the T-score controversy revisited. Current osteoporosis reports. 2014;12(4):403-409.
  46. Binkley N, Kiebzak GM, Lewiecki EM, Krueger D, Gangnon RE, Miller PD, Shepherd JA, Drezner MK. Recalculation of the NHANES database SD improves T-score agreement and reduces osteoporosis prevalence. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2005;20(2):195-201.
  47. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19(4):385-397.
  48. Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2013;16(4):455-466.
  49. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. The Cochrane database of systematic reviews. 2012;7:Cd004143.
  50. Lopez LM, Grimes DA, Schulz KF, Curtis KM, Chen M. Steroidal contraceptives: effect on bone fractures in women. The Cochrane database of systematic reviews. 2014;6:Cd006033.
  51. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporosis International. 2014;25(10):2359-2381.
  52. Clarke BL. New and emerging treatments for osteoporosis. Clinical endocrinology. 2009;71(3):309-321.
  53. Lim V, Clarke BL. New therapeutic targets for osteoporosis: beyond denosumab. Maturitas. 2012;73(3):269-272.
  54. Kling JM, Clarke BL, Sandhu NP. Osteoporosis prevention, screening, and treatment: a review. Journal of women’s health (2002). 2014;23(7):563-572.
  55. Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S. Meta-analysis: excess mortality after hip fracture among older women and men. Annals of internal medicine. 2010;152(6):380-390.
  56. Cawthon PM. Gender differences in osteoporosis and fractures. Clinical orthopaedics and related research. 2011;469(7):1900-1905.
  57. Center JR, Bliuc D, Nguyen ND, Nguyen TV, Eisman JA. Osteoporosis medication and reduced mortality risk in elderly women and men. The Journal of clinical endocrinology and metabolism. 2011;96(4):1006-1014.
  58. Eriksen EF, Diez-Perez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone. 2014;58:126-135.
  59. Modi A, Siris ES, Tang J, Sen S. Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy. Current medical research and opinion. 2015:1-9.
  60. Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C. The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int. 2004;15(12):1003-1008.
  61. Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine & metabolic disorders. 2010;11(4):237-251.
  62. Ornstrup MJ, Kjaer TN, Harslof T, Stodkilde-Jorgensen H, Hougaard DM, Cohen A, Pedersen SB, Langdahl BL. Adipose tissue, estradiol levels, and bone health in obese men with metabolic syndrome. European journal of endocrinology / European Federation of Endocrine Societies. 2015;172(2):205-216.
  63. Beerhorst K, Tan IY, De Krom M, Verschuure P, Aldenkamp AP. Antiepileptic drugs and high prevalence of low bone mineral density in a group of inpatients with chronic epilepsy. Acta neurologica Scandinavica. 2013;128(4):273-280.
  64. Looker AC, Melton LJ, 3rd, Harris TB, Borrud LG, Shepherd JA. Prevalence and trends in low femur bone density among older US adults: NHANES 2005-2006 compared with NHANES III. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010;25(1):64-71.
  65. Bliuc D, Alarkawi D, Nguyen TV, Eisman JA, Center JR. Risk of Subsequent Fractures and Mortality in Elderly Women and Men with Fragility Fractures with and without Osteoporotic Bone Density: The Dubbo Osteoporosis Epidemiology Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2015;30(4):637-646.
  66. Eriksen EF. Treatment of osteopenia. Reviews in endocrine & metabolic disorders. 2012;13(3):209-223.
  67. Tufts G. New treatment approach for osteopenia. Journal of midwifery & women’s health. 2011;56(1):61-67.
  68. Meadows ES, Mitchell BD, Bolge SC, Johnston JA, Col NF. Factors associated with treatment of women with osteoporosis or osteopenia from a national survey. BMC women’s health. 2012;12:1.
  69. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2011;96(7):1911-1930.
  70. Ginde AA, Liu MC, Camargo CA, Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Archives of internal medicine. 2009;169(6):626-632.
  71. LeFevre ML, US Preventive Services Task Force. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. 2015;162(2):133-140.
  72. Binkley N. Vitamin D and osteoporosis-related fracture. Archives of biochemistry and biophysics. 2012;523(1):115-122.
  73. Giangregorio LM, Macintyre NJ, Thabane L, Skidmore CJ, Papaioannou A. Exercise for improving outcomes after osteoporotic vertebral fracture. The Cochrane database of systematic reviews. 2013;1:Cd008618.
  74. Medicine Io. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2010.
  75. Looker AC, Johnson CL, Lacher DA, Pfeiffer CM, Schleicher RL, Sempos CT. Vitamin D status: United States, 2001-2006. NCHS Data Brief. 2011(59):1-8.
  76. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158(6):531-537.
  77. Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Manson JE, Mayne ST, Ross AC, Shapses SA, Taylor CL. IOM committee members respond to Endocrine Society vitamin D guideline. The Journal of clinical endocrinology and metabolism. 2012;97(4):1146-1152.
  78. Gahche J, Bailey R, Burt V, Hughes J, Yetley E, Dwyer J, Picciano MF, McDowell M, Sempos C. Dietary supplement use among U.S. adults has increased since NHANES III (1988-1994). NCHS Data Brief. 2011(61):1-8.
  79. Chandler PD, Giovannucci EL, Williams MA, LeBoff MS, Bates DW, Hicks LS. Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center. The American journal of pharmacy benefits. 2014;6(1):e1-e8.
  80. Shahangian S, Alspach TD, Astles JR, Yesupriya A, Dettwyler WK. Trends in laboratory test volumes for Medicare Part B reimbursements, 2000-2010. Archives of pathology & laboratory medicine. 2014;138(2):189-203.
  81. Winzenberg TM, Powell S, Shaw KA, Jones G. Vitamin D supplementation for improving bone mineral density in children. The Cochrane database of systematic reviews. 2010(10):Cd006944.
  82. Jackson RD, Mysiw WJ. Insights into the epidemiology of postmenopausal osteoporosis: the Women’s Health Initiative. Seminars in reproductive medicine. 2014;32(6):454-462.
  83. Clarke BL. Corticosteroid-induced osteoporosis: an update for dermatologists. American journal of clinical dermatology. 2012;13(3):167-190.
  84. Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS; Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2012;97(6):1802-1822.
  85. Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Archives of internal medicine. 2005;165(14):1618-1623.
  86. Nieves JW, Cosman F, Grubert E, Ambrose B, Ralston SH, Lindsay R. Skeletal effects of vitamin D supplementation in postmenopausal black women. Calcified tissue international. 2012;91(5):316-324.
  87. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014;383(9912):146-155.
  88. Heaney RP, Holick MF. Why the IOM recommendations for vitamin D are deficient. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(3):455-457.
  89. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clinic proceedings. 2011;86(1):50-60.
  90. Moyer VA, Force USPST. Prevention of falls in community-dwelling older adults: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. 2012;157(3):197-204.
  91. Moyer VA, US Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. 2013;158(9):691-696.
  92. Khan A, Bilezikian J. Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2000;163(2):184-187.
  93. Griebeler ML, Kearns AE, Ryu E, Hathcock MA, Melton LJ, 3rd, Wermers RA. Secular trends in the incidence of primary hyperparathyroidism over five decades (1965-2010). Bone. 2015;73:1-7.
  94. Fraser WD. Hyperparathyroidism. Lancet. 2009;374(9684):145-158.
  95. Silverberg SJ, Walker MD, Bilezikian JP. Asymptomatic primary hyperparathyroidism. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2013;16(1):14-21.
  96. Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Monteiro R, Mino J, Swagel W, Mitchell JC. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery. 2013;154(6):1232-1237; discussion 1237-1238.
  97. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, Haigh PI, Adams AL. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. The Journal of clinical endocrinology and metabolism. 2013;98(3):1122-1129.
  98. Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O’Fallon WM, Melton LJ 3rd. Survival after the diagnosis of hyperparathyroidism: a population-based study. The American journal of medicine. 1998;104(2):115-122.
  99. Clifton-Bligh PB, Nery ML, Supramaniam R, Reeve TS, Delbridge L, Stiel JN, McElduff A, Wilmshurst EG, Robinson BG, Fulcher GR, Learoyd D, Posen S. Mortality associated with primary hyperparathyroidism. Bone. 2015;74:121-124.
  100. Schneider DF, Burke JF, Ojomo KA, Clark N, Mazeh H, Sippel RS, Chen H. Multigland disease and slower decline in intraoperative PTH characterize mild primary hyperparathyroidism. Annals of surgical oncology. 2013;20(13):4205-4211.
  101. Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. The Journal of clinical endocrinology and metabolism. 2014;99(10):3561-3569.
  102. Cusano NE, Silverberg SJ, Bilezikian JP. Normocalcemic primary hyperparathyroidism. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2013;16(1):33-39.
  103. Silverberg SJ, Clarke BL, Peacock M, Bandeira F, Boutroy S, Cusano NE, Dempster D, Lewiecki EM, Liu JM, Minisola S, Rejnmark L, Silva BC, Walker MD, Bilezikian JP. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. The Journal of clinical endocrinology and metabolism. 2014;99(10):3580-3594.
  104. Macfarlane DP, Yu N, Leese GP. Subclinical and asymptomatic parathyroid disease: implications of emerging data. The lancet. Diabetes & endocrinology. 2013;1(4):329-340.
  105. Khan AA. Medical management of primary hyperparathyroidism. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2013;16(1):60-63.
  106. Lewiecki EM. Management of skeletal health in patients with asymptomatic primary hyperparathyroidism. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2010;13(4):324-334.
  107. Dillon ML, Frazee LA. Cinacalcet for the treatment of primary hyperparathyroidism. American journal of therapeutics. 2011;18(4):313-322.
  108. Norlen O, Wang KC, Tay YK, Johnson WR, Grodski S, Yeung M, Serpell J, Sidhu S, Sywak M, Delbridge L. No Need to Abandon Focused Parathyroidectomy: A Multicenter Study of Long-term Outcome After Surgery for Primary Hyperparathyroidism. Annals of surgery. 2014.
  109. Schneider DF, Mazeh H, Sippel RS, Chen H. Is minimally invasive parathyroidectomy associated with greater recurrence compared to bilateral exploration? Analysis of more than 1,000 cases. Surgery. 2012;152(6):1008-1015.
  110. Bilezikian JP, Khan A, Potts JT, Jr., Brandi ML, Clarke BL, Shoback D, Jüppner H, D’Amour P, Fox J, Rejnmark L, Mosekilde L, Rubin MR, Dempster D, Gafni R, Collins MT, Sliney J, Sanders J. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(10):2317-2337.
  111. Clarke BL. Bone disease in hypoparathyroidism. Arquivos brasileiros de endocrinologia e metabologia. 2014;58(5):545-552.
  112. Powers J, Joy K, Ruscio A, Lagast H. Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;28(12):2570-2576.
  113. Kundel A, Thompson GB, Richards ML, Qiu LX, Cai Y, Schwenk FW, Lteif AN, Pittock ST, Kumar S, Tebben PJ, Hay ID, Grant CS. Pediatric endocrine surgery: a 20-year experience at the Mayo Clinic. The Journal of clinical endocrinology and metabolism. 2014;99(2):399-406.
  114. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Postsurgical hypoparathyroidism – risk of fractures, psychiatric diseases, cancer, cataract, and infections. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(11):2504-2510.
  115. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. The Epidemiology of Non-Surgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2015.
  116. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;28(11):2277-2285.
  117. Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, Burnett-Bowie SA, Mannstadt M. Long-term follow-up of patients with hypoparathyroidism. The Journal of clinical endocrinology and metabolism. 2012;97(12):4507-4514.
  118. Cusano NE, Rubin MR, McMahon DJ, Irani D, Anderson L, Levy E, Bilezikian JP. PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. The Journal of clinical endocrinology and metabolism. 2014;99(10):3694-3699.
  119. Rubin MR, Sliney J, Jr., McMahon DJ, Silverberg SJ, Bilezikian JP. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int. 2010;21(11):1927-1934.
  120. Cusano NE, Rubin MR, McMahon DJ, Irani D, Tulley A, Sliney J Jr, Bilezikian JP. The effect of PTH(1-84) on quality of life in hypoparathyroidism. The Journal of clinical endocrinology and metabolism. 2013;98(6):2356-2361.
  121. Sikjaer T, Rolighed L, Hess A, Fuglsang-Frederiksen A, Mosekilde L, Rejnmark L. Effects of PTH(1-84) therapy on muscle function and quality of life in hypoparathyroidism: results from a randomized controlled trial. Osteoporos Int. 2014;25(6):1717-1726.
  122. Singer FR, Bone HG, 3rd, Hosking DJ, Lyles KW, Murad MH, Reid IR, Siris ES; Endocrine Society. Paget’s Disease of Bone: An Endocrine Society Clinical Practice Guideline. The Journal of clinical endocrinology and metabolism. 2014;99(12):4408-4422.
  123. Klinck R, Laberge G, Bisson M, McManus S, Michou L, Brown JP, Roux S. Alternative splicing in osteoclasts and Paget’s disease of bone. BMC medical genetics. 2014;15:98.
  124. Ralston SH, Albagha OM. Genetics of Paget’s disease of bone. Current osteoporosis reports. 2014;12(3):263-271.
  125. Bolland MJ, Cundy T. Paget’s disease of bone: clinical review and update. Journal of clinical pathology. 2013;66(11):924-927.
  126. Galson DL, Roodman GD. Pathobiology of Paget’s Disease of Bone. Journal of bone metabolism. 2014;21(2):85-98.
  127. Griz L, Bandeira F, Diniz ET, Cabral M, Freese E. Prevalence of vitamin D deficiency is higher in patients with Paget’s disease of bone compared with age-matched controls. Arquivos brasileiros de endocrinologia e metabologia. 2013;57(7):509-512.
  128. Wat WZ, Cheung WS, Lau TW. A case series of Paget’s disease of bone in Chinese. Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine. 2013;19(3):242-248.
  129. Wat WZ. Current perspectives on bisphosphonate treatment in Paget’s disease of bone. Therapeutics and clinical risk management. 2014;10:977-983.
  130. Maricic M. Zoledronic acid for Paget’s disease of bone. Drugs of today (Barcelona, Spain : 1998). 2007;43(12):879-885.
  131. Keating GM, Scott LJ. Zoledronic acid: a review of its use in the treatment of Paget’s disease of bone. Drugs. 2007;67(5):793-804.
  132. Tziomalos K, Florentin M, Krikis N, Perifanis V, Karagiannis A, Harsoulis F. Persistent effect of zoledronic acid in Paget’s disease. Clinical and experimental rheumatology. 2007;25(3):464-466.
  133. Ruggieri P, Calabro T, Montalti M, Mercuri M. The role of surgery and adjuvants to survival in Pagetic osteosarcoma. Clinical orthopaedics and related research. 2010;468(11):2962-2968.
  134. Gattineni J, Baum M. Regulation of phosphate transport by fibroblast growth factor 23 (FGF23): implications for disorders of phosphate metabolism. Pediatric nephrology (Berlin, Germany). 2010;25(4):591-601.
  135. Mornet E. Hypophosphatasia. Orphanet J Rare Dis. 2007;2:40.
  136. Bianchi ML. Hypophosphatasia: an overview of the disease and its treatment. Osteoporos Int. 2015.
  137. Fraser D. Hypophosphatasia. The American journal of medicine. 1957;22(5):730-746.
  138. Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocrine reviews. 1994;15(4):439-461.
  139. Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millán JL, Skrinar AM, Crine P, Landy H. Enzyme-replacement therapy in life-threatening hypophosphatasia. The New England journal of medicine. 2012;366(10):904-913.
  140. Fukumoto S. [Disorders of phosphate metabolism]. Rinsho byori. The Japanese journal of clinical pathology. 2010;58(3):225-231.
  141. Yuan Q, Sitara D, Sato T, Densmore M, Saito H, Schüler C, Erben RG, Lanske B. PTH ablation ameliorates the anomalies of Fgf23-deficient mice by suppressing the elevated vitamin D and calcium levels. Endocrinology. 2011;152(11):4053-4061.
  142. Clarke BL. FGF23 regulation of phosphorus homeostasis is dependent on PTH. Endocrinology. 2011;152(11):4016-4018.
  143. Calvo MS, Uribarri J. Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population. The American journal of clinical nutrition. 2013;98(1):6-15.
  144. Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine. 2002;4(4):301-306.
  145. Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part II. Disorders. Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine. 2002;4(4):307-315.

Back to Top