Doctor: It’s not just a wrist fracture … your bone mineral density test at your hip indicated that you have osteoporosis because your T-score is below minus 2.5.^1,2

Having this first fracture increases your risk for having another fracture in the future which could be at a different site.^1,2

All of your other tests were normal. I recommend you start treatment for your osteoporosis.

Patient thought bubble 1 (read in a whispering voice by patient): Osteoporosis? I don’t know, that fall was an accident. I just need to focus on healing my wrist and then I’ll be more careful.^3-5

Patient comment bubble 1 (read in a regular voice by patient): I have seen media reports about the side effects of those treatments.^3-5 I need to do more research … I don’t want to start treatment just yet.^3-5

Thought bubble 1 (read in a quiet / frustrated voice by doctor): Why didn’t she accept my recommendation?

Thought bubble (read in a whispering voice by doctor): I should re-read those notes from that article about communication strategies that help osteoporosis patients understand their diagnosis and the benefits and risks of treatment.³

Understand, acknowledge and discuss your patient's concerns, but also ensure they understand that osteoporosis is a real disease that weakens their bones and makes them more likely to break.^1,6

While the fears of treatment side effects are real, ensure your patient understands that osteoporosis is a chronic disease and for many, the risks of the disease outweigh the risks of treatment.¹

When discussing treatment options and the potential for adverse events...consider presenting statistics in an understandable way by using absolute numbers and visual aids.¹

Present information in multiple forms to improve your patient’s understanding, and retention of key details.¹

Encourage your patient to ask questions which promotes shared decision making and helps to identify what's most important to the patient and barriers to management.^1,7

Include lifestyle modifications as part of the overall treatment plan to help counter the concern some patients may have that physicians view medication as the only solution and help your patient feel more proactive about their treatment.^1,8

References

1. Camacho PM, et al. Endocr Pract. 2016;22(Suppl 4):1-42.
2. Siris ES, et al. JAMA. 2001;286:2815-2822.
3. Besser SJ, et al. Arch Osteoporos. 2012;7:115-124.
4. Cadarette SM, et al. Curr Opin Rheumatol. 2010;22:397-403.
5. Sambrook PN, et al. Med J Aust. 2010;193:154-156.
6. Güss CD, et al. Front Psychol. 2017;8:851.
7. Iversen MD, et al. Geriatr Phys Ther. 2011;34(2):72-81.
8. The Peter Sandman Risk Communication Website. www.psandman.com/articles/covello.htm. Accessed February 13, 2018.

A fragility fracture, also referred to as a low-trauma fracture, occurs every 3 seconds worldwide.¹

The occurrence of a fragility fracture reveals underlying skeletal weakness or osteoporosis.²

And is a strong predictor of future fracture risk.^2,3

In general, there is a lack of public awareness about osteoporosis and a misconception that it is an unavoidable part of aging.^4-6

Osteoporosis is more prevalent than you think. Approximately 200 million women worldwide are affected by osteoporosis.¹

And worldwide 1 in 3 women over 50 years of age will suffer a fragility fracture.¹

However, fewer than 1 in 5 may be evaluated for osteoporosis.^5,7-9

And fewer than 1 in 3 may be treated, even after experiencing a fragility fracture.^10-17

These are poor rates of management, especially when compared to rates of monitoring, screening and treatment in other chronic diseases.⁷

Fragility fractures at various sites are associated with significant clinical and personal burden.^18-26

This may include: difficulty performing activities of daily living,^18,20,21 admission to long-term care facilities,¹⁸ pain or complications from hospitalization,^19,20 worry - which can impact relationships²⁶ and financial burden for patients and caregivers.²⁶

Functional autonomy and independence are highly valued by patients at risk of hip fracture.²⁷

Fragility fractures result in more hospitalizations than breast cancer, stroke or myocardial infarction.²⁸

A prior fragility fracture can substantially increase the relative risk of a future fracture.^2,3,29-31

And, the subsequent fracture can occur at the same or a different site from the initial fracture.³

There is a crisis in osteoporosis.

The downward trend in hip fracture incidence has hit a plateau, meaning fewer patients at high risk for fracture are managed appropriately.³²

Organizations across the globe are supporting a call to action to intensify efforts to prevent fracture.

Worldwide there are specific activities supporting the call to action.³³

References

1. International Osteoporosis Foundation. Facts and statistics. www.iofbonehealth.org/facts-statistics. Accessed February 13, 2018.
2. Kanis JA, et al. Bone. 2004;35:375-382.
3. Center JR, et al. JAMA. 2007;297:387-394.
4. Besser SJ, et al. Arch Osteoporos. 2012;7:115-124.
5. Boudreau DM, et al. J Am Geriatr Soc. 2017;65:1829-1835.
6. National Osteoporosis Foundation. NOF in the News. https://www.nof.org/category/nof-in-the-news/ Published August 10, 2017.
7. Medica. Clinical Performance Measures Report 2012-2013. www.medica.com/-/media/documents/quality/ cpm_report_member.pdf. Accessed February 28, 2018.
8. Fast Facts. Osteoporosis Canada. https://osteoporosis.ca/about-the-disease/fast-facts/
9. Nguyen TV, et al. Med J Aust. 2004;180:S18-22.
10. Yusuf AA, et al. Arch Osteoporos. 2016;11:31.
11. Spångéus A, et al. Ann Rheum Dis. 2017;76(suppl2):72.
12. Sanfélix-Genovés J, et al. Osteoporos Int. 2013;24:1045-1055.
13. Hadji P, et al. Dtsch Arztebl Int. 2013;110(4):52-7.
14. Viprey M, et al. PLoS ONE. 2015;10(12):e0143842.
15. Bell JS, et al. Aust Fam Physician. 2012;41:110-118.
16. Eisman J, et al. J Bone Miner Res. 2004;19:1969-75.
17. Taiwanese Guidelines for Prevention and Treatment of Osteoporosis. Taiwanese Osteoporosis Association, 2013.
18. Bentler SE, et al. Am J Epidemiol. 2009;170:1290-1299.
19. Inacio MCS, et al. Perm J. 2015;19:29-33.
20. Cosman F, et al. Osteoporos Int. 2014;25:2359-2381.
21. Mulcahy A, et al. Presented at: ASBMR annual meeting; October 16-18, 2016; Atlanta, GA. Abst MO0243.
22. Palacios S, el al. Climacteric. 2014;17:60-70.
23. Abimanyi-Ochom J, et al. Osteoporos Int. 2015;26:1781-1790.
24. Dyer SM, et al. BMC Geriatr. 2016;16158
25. Fechtenbaum J, et al. Osteoporos lnt. 2005;16:2175-2179.
26. National Osteoporosis Society. Life with osteoporosis. October 2014. https://nos.org.uk/media/1859/life-with-osteoporosis.pdf. Accessed February 14, 2018.
27. Salkeld G, et al. BMJ. 2000;320:341-346.
28. Singer A, et al. Mayo Clin Proc. 2015;90:53-62.
29. van Geel TA, et al. Ann Rheum Dis. 2009;68:99-102.
30. Klotzbuecher CM, et al. J Bone Miner Res. 2000;15(4):721-739.
31. Gehlbach S, et al. J Bone Miner Res. 2012;27(3):645-653.
32. Lewiecki EM, et al. Osteoporos Int. 2017.
33. ASBMR. Call to action to address the crisis in the treatment of osteoporosis. www.asbmr.org/call-to-action.aspx. Accessed February 28, 2018.

The human skeleton gives the body its shape and provides physical support for the system contained within.¹ It also forms part of the musculoskeletal system that enables us to move.¹ The structure of bone is optimized so that it is strong but relatively lightweight.

The interior of bone is composed of bone marrow.² It is surrounded by two major types of bone tissue: cortical bone, or the hard outer shell of bone; and trabecular bone, the spongy-looking center.² The amount of each type of tissue in bone is dependent on the function of that bone.²

The basic unit of cortical or compact bone is the osteon.² It is composed of successive concentric lamellae.² This structure contributes to bone strength by resisting bending.²

Cells called osteocytes are distributed within the concentric lamellae.² Osteocytes form a complex network³ that is thought to be important in maintaining the viability and structural integrity of bone.⁴

At the center of the osteon is the Haversian canal. These canals contain blood vessels and nerves.² The blood vessels within bone facilitate the exchange between osteocytes and the blood.²

Trabecular bone is present in the interior of some bones and resists compression.² Osteocytes are also contained within its structure and again play an important role in sensing local changes in strain.⁵ Trabeculae are covered in a layer of flattened lining cells that are thought to be involved in the dynamic process by which bone is formed and broken down.²

Bone marrow is found within the interior of bones. The surrounding trabeculae and vascular network provide structural support, nutrition and a waste removal system for the heterogeneous group of cells found within this space.⁶ Bone marrow is a site for haemopoiesis, the process by which the cellular components of blood are formed.⁶

Bone is a dynamic tissue that is continually being built, broken down and rebuilt in a process called bone remodeling.³

Bone tissue is broken down and resorbed by multinucleated cells known as osteoclasts.³ These cells are derived from monocytes which originate within bone marrow.⁷ Osteoclasts play an important role in liberating minerals and other molecules stored within the bone matrix.^8,9

Bone tissue serves as a repository for vital minerals, including calcium phosphate,⁸ and various biologically active molecules, such as growth factors.⁹ The release of calcium from the bone can play a role in maintaining its homeostasis within the body.⁸

The cells responsible for building new bone tissue are known as osteoblasts.³ Osteoblasts are thought to be derived from cells found to be associated with blood vessels.¹⁰ Once active, they start to produce the organic component of bone osteoid, which is predominantly made of collagen.³

Minerals start to crystallize around the collagen scaffold to form hydroxyapatite, the major inorganic constituent of bone, which contains calcium phosphate.^2,11 Bone mineral density (or BMD) can be used to estimate the strength of bone and to assess the risk of fracture.¹²

As osteoblasts form new bone tissue, many become embedded within the matrix and differentiate into osteocytes.³

The structure, composition and cellular processes that occur within bone allow it to simultaneously serve as a calcium reservoir,⁸ while providing structural support for the vital organs and for locomotion.¹

References

1. Watkins J. The Skeleton. In: Watkins J. Structure and Function of the Musculoskeletal System. Human Kinetics Publishers, Inc;2010:21-58.
2. Nather A, Ong HJC, Aziz Z. Structure of Bone. In: Nather A. Bone Grafts and Bone Substitutes: Basic Science and Clinical Applications. World Scientific Publishing.
3. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285:25103-25108.
4. Vashishth D, Verborgt O, Divine G, et al. Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone. 2000;26:375-380.
5. Adachi T, Kameo Y, Hojo M. Trabecular bone remodelling simulation considering osteocytic response to fluid-induced shear stress. Phil Trans R Soc A. 2010;368:2669-2682.
6. Wilkins BS. Histology of normal haemopoiesis: bone marrow histology I. J Clin Pathol. 1992;45:645-649.
7. Tinkler SMB, Linder JE, Williams DM, et al. Formation of osteoclasts from blood monocytes during 1 alpha-OH Vit D-stimulated bone resorption in mice. J Anat. 1981;133:389-396.
8. Komarova SV. Mathematical model of paracrine interactions between osteoclasts and osteoblasts predicts anabolic action of parathyroid hormone on bone. Endocrinology. 2005;146:3589-3595.
9. Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Res. 2005;15:57-62.
10. Doherty MJ, Ashton BA, Walsh S, et al. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res. 1998;13:828-838.
11. Simão AMS, Yadav MC, Ciancaglini P, et al. Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization. Braz J Med Biol Res. 2010;43:234-241.
12. Hanssens L, Reginster JY. Relevance of bone mineral density, bone quality and falls in reduction of vertebral and non-vertebral fractures. J Musculoskelet Neuron Interact. 2003;3:189-193.

Accidents happen.

But after a simple fall from standing height,^1,2 the difference between a momentary mishap and a fracture may be more than an accident^3-5 and is potentially a result of compromised bone strength.^3-5 A fragility fracture, also often referred to as a low-trauma fracture,^1,5,6 could reflect a deficit in bone mass and structural integrity,^5,7 the main determinants of bone strength.⁸ This deficit occurs when bone formation by osteoblasts fails to counterbalance bone resorption by osteoclasts.⁷ Every three seconds, someone in the world experiences a low-trauma clinical fracture,⁹ a fragility fracture that causes immediate pain and disability.^6,10 Clinical fractures happen anywhere in the skeleton and include nonvertebral^2,11 and symptomatic vertebral fractures.⁹ These fractures can result in a substantial burden to individuals and society.¹⁰ Any such fracture signals increased risk for a subsequent clinical fracture.² After a clinical fracture, one in 4 women will sustain another fracture in the next 5 years.¹² A clinical fracture signals a need for immediate action to reduce the risk of further fractures.⁵ Improving bone mass, structure, and strength can help protect against further fractures.^5,7

The skeleton is a dynamic organ with a capacity to change its mass and structure^7,13 by way of multiple signaling pathways that regulate bone formation and resorption.^13-15 Extensive crosstalk among osteocytes, osteoblasts, and osteoclasts affects signaling via these pathways.¹⁴ Osteocytes can limit bone formation by secreting Wnt antagonists.¹⁶ Of these, sclerostin is a key negative regulator of bone formation in adults.^14,17 Under conditions of reduced weight bearing¹⁸ or postmenopausal estrogen deficiency,^19,20 osteocytes secrete more sclerostin. At the cellular level, sclerostin interferes with Wnt coreceptor signaling,^18,21 thus reducing the amount of new bone being formed by osteoblasts.¹⁸ Sclerostin also increases osteoclast formation and resorptive activity indirectly by increasing the expression of RANKL and decreasing the expression of OPG in osteoblast lineage cells.²² Under conditions of mechanical loading, as in exercise^23,24 or with PTH^19,23 and estrogen signaling,^19,20 osteocytes secrete less sclerostin, allowing Wnt to bind to its coreceptors,¹⁶ resulting in signaling associated with increased bone formation by osteoblasts.¹⁶ These responses are part of the body’s diverse repertoire for regulating bone mass.¹⁴

References

1. Prentice A, Schoenmakers I, Laskey MA, de Bono S, Ginty F, Goldberg GR. Nutrition and bone growth and development. Proc Nutr Soc. 2006;65:348-60.
2. Center JR, Bliuc D, Nguyen TV, Eisman JA. Risk of subsequent fracture after low-trauma fracture in men and women. JAMA. 2007;297:387-94.
3. Bouxsein ML, Seeman E. Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol. 2009;23:741-53.
4. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005;115:3318-25.
5. Boonen S, Singer AJ. Osteoporosis management: impact of fracture type on cost and quality of life in patients at risk for fracture I. Curr Med Res Opin. 2008;24:1781-8.
6. Abimanyi-Ochom J, Watts JJ, Borgström F, et al. Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS). Osteoporos Int. 2015;26:1781-90.
7. Seeman E, Delmas PD. Bone quality: the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250-61.
8. Seeman E. Bone quality: the material and structural basis of bone strength. J Bone Miner Metab. 2008;26:1-8.
9. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17:1726-33.
10. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004.
11. van Helden S, Cals J, Kessels F, Brink P, Dinant GJ, Geusens P. Risk of new clinical fractures within 2 years following a fracture. Osteoporos Int. 2006;17:348-54.
12. Bliuc D, Nguyen ND, Nguyen TV, Eisman JA, Center JR. Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men. J Bone Miner Res. 2013;28:2317-24.
13. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285:25103-8.
14. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179-92.
15. Blau JE, Collins MT. The PTH-Vitamin D-FGF23 axis. Rev Endocr Metab Disord. 2015;16:165-74.
16. Robling AG, Niziolek PJ, Baldridge LA, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283:5866-75.
17. van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199:805-14.
18. Lin C, Jiang X, Dai Z, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24:1651-61.
19. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95:1991-7.
20. Jia HB, Ma JX, Ma XL, et al. Estrogen alone or in combination with parathyroid hormone can decrease vertebral MEF2 and sclerostin expression and increase vertebral bone mass in ovariectomized rats. Osteoporos Int. 2014;25:2743-54.
21. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280:19883-7.
22. Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One. 2011;6(10):e25900.
23. Ke HZ, Richards WG, Li X, Ominsky MS. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33:747-83.
24. Kontulainen S, Sievänen H, Kannus P, Pasanen M, Vuori I. Effect of long-term impact- loading on mass, size, and estimated strength of humerus and radius of female racquet- sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res. 2002;17:2281-9.

Discoveries in bone biology have revealed the role of the RANK ligand pathway in osteoclast-mediated bone loss and postmenopausal osteoporosis.

Osteoporosis is a significant health burden, compromising the strength of bones and increasing the risk for fracture.

Menopause is a key turning point in the skeletal health of women.

Following menopause, declines in estrogen often lead to excessive bone remodeling activity and accelerated bone loss.

Bone loss following menopause results from an imbalance of osteoclast and osteoblast activity.

Osteoclasts are the specialized cells that resorb bone, and osteoblasts are the cells that form new bone.

The discovery of the RANK ligand pathway has been an important advance in our understanding of bone remodeling.

RANK ligand, a protein expressed by osteoblasts, plays a key role in osteoclast formation, function, and survival through interaction with its receptor, RANK, that is expressed on the surface of osteoclasts.

Osteoprotegerin, or OPG, another protein secreted by osteoblasts, is a natural inhibitor of RANK ligand and plays a role in regulating bone resorption.

At the initiation of bone remodeling, lining cells move apart to expose the bone surface, become osteoblasts, and begin expressing RANK ligand.

RANK ligand binds to RANK on osteoclast precursors, which initiates cell fusion and the formation of mature, multinucleated osteoclasts.

RANK ligand continues to bind to RANK on mature osteoclasts.

The binding of RANK ligand to RANK is essential for osteoclast formation, function, and survival.

Following bone resorption, osteoblasts migrate into the pit.

Osteoblasts fill the pit with new bone matrix.

Some osteoblasts become embedded within the matrix and eventually turn into osteocytes, while others become new lining cells on the bone surface.

In the final stage of remodeling, newly created bone matrix mineralizes and the bone returns to a resting state.

The process of bone remodeling is regulated by factors including estrogen and OPG.

Estrogen limits the amount of RANK ligand expression by osteoblasts and OPG blocks the binding of RANK ligand to RANK, thereby reducing osteoclast activity.

In postmenopausal women, reduced levels of estrogen lead to increased expression of RANK ligand by osteoblasts.

Excessive RANK ligand overwhelms OPG, leading to more osteoclasts, increased bone remodeling activity, and greater bone loss.

Osteoblasts continue to deposit new bone matrix, but they can not replace all of the resorbed bone. Therefore, resorption pits may not be completely refilled, which over time leads to thinning and weakening of bone.

The progressive loss of bone following menopause reduces the structural integrity and strength of the skeleton.

Bone loss may go undetected for many years until the occurrence of a fracture, a potentially serious and debilitating outcome of postmenopausal osteoporosis.

In summary, in postmenopausal women, as estrogen declines, RANK ligand expression increases. Elevated RANK ligand levels lead to increased osteoclast formation, function and survival. Greater osteoclast activity increases bone loss, weakens bone architecture, and can ultimately lead to fracture.

We now understand the underlying biological mechanism of the increase in bone resorption that follows menopause.

RANK ligand is a key link between reduced estrogen levels and osteoclast-mediated bone loss.

References

Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol. 2005;5:618-625.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337-342.
US Department of Health and Human Services: Bone Health and Osteoporosis: A Report of the Surgeon General. Washington DC.F 2004.
Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. 2005;20:177-184.
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005;115:3318-3325.
Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250-2261.
Chavassieux P, Seeman E, Delmas PD. Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev. 2007;28:151-164.
Morgan EF, Barnes GL, Einhorn TA. The Bone Organ System: Form and Function. In: Marcus R, Feldman D, Nelson DA, Rosen CJ, eds. Osteoporosis. 3rd ed. New York, NY: Elsevier Academic Press; 2008:3-25.
Lacey DL, Tan HL, Lu J, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol. 2000;157:435-448.
Dempster DW. Anatomy and Functions of the Adult Skeleton. In: Favus M, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: ASBMR; 2006:7-11.
Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003;111:1221-1230.
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785-795.
World Health Organization. Technical Report Series 921: Prevention and Management of Osteoporosis: Report of a WHO Scientific Group. Geneva, Switzerland. 2003.
Hodgson SF, Watts NB, Bilezikian JP, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 ed, with selected updates for 2003. Endocr Pract. 2003;9:544-564.
Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29:155-192.

The skeleton changes across the human life span. This is characterized predominantly by bone formation and growth throughout childhood, followed by a gradual loss of bone density that begins in early adulthood that can accelerate significantly in older adults.^1,2

The density of bone is modulated by a group of cells including osteoclasts, which are multinucleated cells that resorb bone, and osteoblasts, which refill the resorption cavities created by osteoclasts.³

Osteoclasts anchor themselves to the surface of bone.³ This creates a microenvironment underneath the cell, which is referred to as the “sealed zone”.

Within this zone, the osteoclasts create an acidic environment that dissolves the bone’s mineral content.³ Once the mineral content of the bone has been dissolved, enzymes released from osteoclasts remove the remaining collagenous bone matrix to complete the process of resorption.^3,4

Following resorption, osteoblasts move into the resorption space and start to produce and deposit organic matrix called osteoid. Osteoid, a substance made predominantly of collagen, forms a scaffold in which minerals, including calcium and phosphate, begin to crystallize.^3,5,6 Some active osteoblasts become trapped within the matrix they secrete, and thereby become osteocytes.³

Other osteoblasts will undergo apoptosis or will revert back to lining cells which cover the surface of bone.³

This cycle of bone resorption and formation is referred to as remodeling. There is also a process where bone formation by osteoblasts occurs without prior bone resorption by osteoclasts; this results in an increase in bone mass and is referred to as bone modeling.⁷ Bone modeling promotes the growth of bones and is important for maintaining bone strength.⁷

Remodeling also plays an important role during bone growth by optimizing the growing structure.⁷

After the age of 30, most people experience a gradual loss in bone mass due to a relative decrease in the activity of osteoblasts compared with osteoclasts.¹ However, there are many factors that impact the process of bone remodeling and influence the degree of bone loss we experience as we age. For example, medications, such as glucocorticoids, which can promote osteoclast activity and also reduce bone formation.^8-10

Proper nutrition and physical activity can help strengthen bone.^8,9 It is also believed that osteocytes form a complex network in bone that can sense any increased work load on the bone and respond by triggering the differentiation and activity of osteoblasts to increase bone density.^9,11

Conversely, when bone experiences reduced loading conditions, such as during long term bed rest, resorption and remodeling increase to eliminate underloaded bone.^9,11,12

Loss of bone mass reduces its strength and increases the risk of fracture.¹ This highlights the importance of staying active, maintaining good nutrition throughout life, and being aware of personal risk factors associated with low bone density.^8,9

References

1. van der Linden JC, Homminga J, Verhaar JAN, et al. Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res. 2001;16:457-465.
2. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004.
3. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285:25103-25108.
4. Saftig P, Hunziker E, Wehmeyer O, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A. 1998;95:13453-13458.
5. Nather A, Ong HJC, Aziz Z. Structure of Bone. In: Nather A. Bone Grafts and Bone Substitutes: Basic Science and Clinical Applications. World Scientific Publishing Company; 2005:3-18
6. Simão AMS, Yadav MC, Ciancaglini P, et al. Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization. Braz J Med Biol Res. 2010;43:234-241.
7. Seeman E. Osteocytes--martyrs for integrity of bone strength. Osteoporos Int. 2006;17:1443-1448.
8. Prentice A, Schoenmakers I, Laskey MA, et al. Nutrition and bone growth and development. Proc Nutr Soc. 2006;65:348-360.
9. Bergmann P, Body JJ, Boonen S, et al. Loading and skeletal development and maintenance. J Osteoporos. 2010;2011:786752.
10. Jia D, O'Brien CA, Stewart SA, et al. Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology. 2006;147:5592-5599.
11. Moester MJC, Papapoulos SE, Löwik CWGM, et al. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2007;87:99-107.
12. Zerwekh JE, Ruml LA, Gottschalk F, et al. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res. 1998;13:1594-1601.

Osteoporosis is chronic and progressive in nature; when untreated there is ongoing bone loss contributing to a weakened skeleton and increased risk of fracture.¹

Bone mass decreases gradually after achieving its peak at 30 years of age.^2,3

After menopause, there can be accelerated loss of both trabecular and cortical bone ongoing with age⁴ that compromises bone strength and predisposes to fracture.

This is what healthy bone looks like at age 35. As bone loss progresses with age it continues to deteriorate in structural integrity.^5,6

Here is a bone at age 44.^5,6

Here is a bone at age 51.^5,6

Here is a bone at age 65.^5,6

Progressive bone loss is a key contributor to increased fracture risk with age.^5,6

This is the bone structure of a 74-year-old female who suffered an osteoporotic hip fracture.^5,6

For patients with osteoporosis, a timely diagnosis and appropriate treatment can reduce the risk of fractures.

References

1. Hanley DA, et al. Am J Med. 2017;130:862.e1-862.e7.
2. Zebaze RM, et al. Lancet. 2010;375:1729-1736.
3. Recker RR, et al. JAMA. 1992;268(17):2403-2408.
4. Khosla S, et al. Endocrinol Metab Clin North Am. 2005;34:1015-1030.
5. Muller R. Osteoporos Int. 2005;16(Suppl 2):S25-S35.
6. Schulte FA, et al. Bone. 2011;49:1166-1172.

Over 200 million women worldwide are affected by osteoporosis.¹

However, fewer than 1 in 5 women with postmenopausal osteoporosis will be evaluated.^2-4

And fewer than 1 in 3 postmenopausal women with osteoporosis are treated.^5-13

Obtain a DXA scan in all women ≥ 65 and women older than 50 who have clinical risk factors for osteoporosis.^14-17

Understanding clinical risk factors for osteoporosis and fracture risk can help in formulating the best questions to ask your patients for accurate screening and diagnosis.^14-18 Questions to consider asking your patients might be: Have you ever experienced a fracture? Has anyone in your family? Have you had any recent falls? Do you have prolonged unusual back pain? A yes, could indicate a vertebral fracture. Are you taking medications that increase bone loss like glucocorticoids? Or are you taking medications that increase your risk of falling like narcotic analgesics? Have you experienced significant weight loss? Do you consume alcohol or tobacco? Are you getting adequate calcium and vitamin D in your diet? What is your level of activity?¹⁸

In addition to asking these questions, on your clinical examination, look for kyphosis^14,17,18 or height loss^14-18 which are signs of osteoporosis, or difficulty performing the get up and go test which indicates risk for falls.¹⁹ Further, in patients at risk, consider spine x-rays to identify unrecognized vertebral fractures and consider adding "rule out vertebral fracture" to imaging orders.^15,16

Bone mineral density alone does not explain all fragility fracture risk. In fact 60% of women with fragility fractures have non-osteoporotic bone mineral density (T-score >-2.5).^14,20,21 Understanding clinical risk factors and BMD together improve fracture risk prediction²¹ in these patients.

Determining a patient's fracture risk requires consideration of several clinical risk factors of which a history of prior fracture, older age, and low bone mineral density are most important, followed by other non-modifiable and modifiable risk factors.^16,22-25

Some non-modifiable risk factors influencing a patient's fracture risk include: family history of hip fracture or osteoporosis, female sex, Asian or white ethnicity, small frame, comorbid conditions.^16,23-25 While some modifiable risk factors include: estrogen deficiency, fall-related risk factors and inadequate physical activity.^16,23

There are several methods you can use to identify women over age 50 at high risk for fracture that need treatment. Patients with a history of fracture at the hip or spine are at a high risk for future fracture.^16,26

Women over age 50 with bone mineral density T-scores below -2.5 are considered osteoporotic and at high risk for future fracture.²⁶

High risk patients are those women with FRAX 10-year probability of hip fracture ≥ 3%, or 10-year probability of major osteoporotic fracture ≥ 20%.²⁶

Fragility fractures at the proximal humerus, pelvis, and in some cases wrist qualify patients as high risk for future fracture, when occurring in combination with low bone mineral density at the hip or spine.²⁶ Please note that regional thresholds and criteria for treatment eligibility may vary.

References

1. International Osteoporosis Foundation. Facts and statistics. www.iofbonehealth.org/facts-statistics. Accessed February 13, 2018.
2. Boudreau DM, et al. J Am Geriatr Soc. 2017;65:1829-1835.
3. Fast Facts. Osteoporosis Canada. https://osteoporosis.ca/about-the-disease/fast-facts/.
4. Nguyen TV, et al. Med J Aust. 2004;180:S18-22.
5. Yusuf AA, et al. Arch Osteoporos. 2016;11:31.
6. Spångéus A, et al. Ann Rheum Dis. 2017;76(suppl2):72.
7. Sanfélix-Genovés J, et al. Osteoporos Int. 2013;24:1045-1055.
8. Hadji P, et al. Dtsch Arztebl Int. 2013;110(4):52-7.
9. Viprey M, et al. PLoS ONE. 2015;10(12):e0143842.
10. Bell JS, et al. Aust Fam Physician. 2012;41:110-118.
11. Eisman J, et al. J Bone Miner Res. 2004;19:1969-75.
12. Taiwanese Guidelines for Prevention and Treatment of Osteoporosis. Taiwanese Osteoporosis Association, 2013.
13. Boytsov NN, et al. Am J Med Qual. 2017;32(6):644-654.
14. Camacho PM, et al. Endocr Pract. 2016;22(suppl 4):1-42.
15. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.
16. Cosman F, et al. Osteoporos Int. 2014;25:2359-2381.
17. Kanis JA, et al. Osteoporos Int. 2013;24:23-57.
18. Orimo H, et al. Arch Osteoporos. 2012;7:3-20.
19. Vondracek SF, et al. Clin lnterv Aging. 2009;4:121-136.
20. Siris ES, el al. JAMA. 2001;286:2815-2822.
21. Siris ES, et al. Arch Intern Med. 2004;164:1108-1112.
22. Kanis JA, et al. Bone. 2004;35:375-382.
23. Kanis JA, et al. Lancet. 2002;359:1929-1936.
24. Eisman JA, et al. J Bone Miner Res. 2012;27:2039-2046.
25. US Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. 2004. Rockville, MD.
26. Siris ES, et al. Osteoporos Int. 2014;25:1439-1443.