Osteoporosis

Definition

Progressive skeletal disorder characterized by low bone mass, deterioration of bone tissue and disruption of bone architecture leading to compromised bone strength and increase in the risk of fractures.

Etiology

Epidemiology

Pathophysiology

Clinical Presentation

• Usually asymptomatic until fracture occurs
• Fractures of the hip, spine, and wrist are most common
• Fragility fractures: Fractures with little or no trauma, such as fall from sitting or standing height, of a low couch or sofa, or fall down 1-3 steps
• Chronic pain is the common post-fracture symptom, especially after vertebral fracture
• Vertebral fracture symptoms
  • Sudden onset of back pain
  • Lying on one’s back makes the pain less intense
  • Limited spinal mobility
  • Loss of height over time
  • Reduced rib-pelvis distance
  • A stooped posture or kyphosis, also called a “dowager’s hump”
  • Standing or walking will usually make the pain worse
• Key risk factors for fall

Differential Diagnosis

Investigation and Workup

• Osteoporosis Canada recommends that all postmenopausal women and men older than 50 years be assessed for the presence of risks factors for osteoporosis
• Postmenopausal women over age 50 years and men who have risk factors for osteoporosis and fracture based on targeted history and physical examination, or those 65 years and older, should undergo screening with DEXA (dual-energy x-ray absorptiometry)
• There are two stages of assessment in identifying high-risk individuals for osteoporosis:
  • Risk factors identifying those who should be assessed with a Bone Mineral Density (BMD) test
  • Risk factors identifying those at risk of osteoporotic (fragility) fracture who should be considered for therapy

History

Identify risk factors for low BMD, future fractures, and falls:

• Prior fragility fractures after age 40 years
• Family history of osteoporotic fracture/ parental hip fracture
• Medication history
  • Such as: glucocorticoid use greater than 3 months in the prior year at a prednisone-equivalent dose of ≥7.5 mg daily
  • Chronic heparin therapy
• Lifestyle factors
  • Current smoking
  • High alcohol intake (≥3 units per day)
  • High caffeine consumption
  • Dietary calcium intake
  • Physical activity
  • Weight loss greater than 10% of weight at age 25
  • Poor nutrition
  • Premature menopause
• Rheumatoid arthritis
• Inquire about falls in the previous 12 months and inquire about gait and balance
• Accurate height and weight measurement
• Get-Up-and-Go Test
  • Inability to rise from a chair without using the arms and walk a few steps and return
• Dementia

Physical exam:

• Measure Weight
  • Weight loss of >10% since age 25 is significant

Screening for vertebral fractures:

• Measure Height
• Measurement of height loss is a good clinical indicator of vertebral fracture
  • Historical height loss >6 cm (difference between the tallest recalled height and current measured height) OR
  • Prospective height loss of 2 cm (from two or more office visits within 3 years)
• Measure rib to pelvis distance
  • ≤2 fingers’ breadth in vertebral fractures
• Measure occiput-to-wall distance and kyphosis
  • Measure the distance between the wall and the patient’s occiput as the individual stands straight with heels and back against the wall. Vertebral fractures should be suspected if the distance between the wall and the occiput >5 cm

Laboratory:

For all patients with osteoporosis:

• Calcium corrected for albumin
• Complete blood count (CBC)
• Creatinine
• Alkaline phosphatase
• Thyroid-stimulating hormone
• Serum protein electrophoresis (for patients with vertebral fractures)
• 25-Hydroxyvitamin D* – measure in patients with:
  • Recurrent fractures
  • Bone loss despite osteoporosis treatment
  • Co-morbid conditions that affect vitamin D absorption or action
• *Should be re-measured after three to four months of adequate supplementation and should not be repeated if an optimal level (at least 75 nmol/L) is achieved.

In selected patients based on clinical assessment, additional biochemical testing may be required to rule out secondary causes of osteoporosis, such as:

• Serum testosterone
• Urinary free cortisol
• Vitamin B12 level and intrinsic factor antibody
• Antigliadin and anti-endomysial antibodies
• Serum phosphate
• 24-hour urinary calcium

Imaging:

Plain X-rays:

• Simple x-rays of bones are not very accurate in predicting whether someone is likely to have osteoporosis
• May show decreased radiodensity and loss of trabecular structure

Spinal osteoporotic fractures

• Initial assessment is done with antero-posterior (AP) and lateral views of both the thoracic and lumbar spines
• The standard follow-up only consists of single lateral views of the thoracic and lumbar spine that include T4 to L4 vertebrae

Bone mineral density testing:

• Expressed in terms of T-scores and Z-scores
• Based upon the lowest value for lumbar spine (minimum two vertebral levels), total hip, and femoral neck. If either the lumbar spine or hip is invalid, then the forearm should be scanned and the distal 1/3 region reported
• Diagnosis of osteoporosis is derived from the following classification of BMD measures by a WHO Working Group, based on fracture risk:
• From age 50 years or over, the T-score system is appropriate. ” T-score” is the number of standard deviations (SD) the patient’s BMD is above or below the mean value for that of young-adult reference population
  • Normal BMD: T-score between +2.5 and -1.0, inclusive (2.5 SDs above and 1.0 SD below the young adult mean)
  • Osteopenia (low BMD): T-score between -1.0 and -2.5
  • Osteoporosis: T-score ≤ -2.5
  • Severe osteoporosis: T-score ≤ -2.5 plus fragility fracture
• Prior to age 50 years, the age- and sex-matched Z scores are preferred. It is the number of standard deviations below the mean for an age-matched population
  • Below expected range for age: Z-score ≤ -2.0
  • Within expected range for age: Z-score > -2.0
  • Z-score <-2.0 should prompt evaluation for causes of secondary osteoporosis
• Indications for bone mineral density (BMD) testing:

Dual-energy X-ray absorptiometry:

• Measures bone mineral content and bone area
• Currently, DEXA remains the most accurate and widely used tool for BMD measurement of the central skeleton in the clinical setting
• It is used for diagnosis, predicting the relative risk of fracture, and following the effects of treatment for osteoporosis
• Most often performed on the lower spine and hips
• Therapeutic progress using central DEXA should be monitored in clinical settings one or two years after initiating therapy
• Depending on the clinical situation, central DEXA scans (lumbar spine and hip) may be repeated in 1 to 3 years, on the same instrument, using the same procedure

Quantitative computerized tomography (QCT):

• Quantitative computed tomography (QCT) can be used to assess BMD
• Measures volumetric bone density of the spine and hip and can analyze cortical and trabecular bone separately
• In postmenopausal women, QCT measurement of spine trabecular BMD can predict vertebral fractures, whereas pQCT of the forearm at the ultra-distal radius predicts hip but not spine fractures
• There is lack of sufficient evidence for fracture prediction in men

Quantitative ultrasound (QUS):

• Radiation-free technique used to examine bone in the calcaneus (heel), tibia, patella, and other peripheral skeletal sites for two values:
  • The speed of sound in bone (SOS)
  • Broadband ultrasound attenuation (BUA)
• Both the SOS and BUA are higher in healthy bone than in osteoporotic bone
• Validated heel QUS devices predict fractures in
  • Postmenopausal women (vertebral, hip and overall fracture risk)
  • Men 65 years and older (hip and non-vertebral fractures)

Peripheral measurements:

These technologies can only be used to predict fractures. Often measure BMD at several skeletal sites, such as radius, phalanx, calcaneus, tibia, metatarsal.

Ultrasound

• Uses sound waves to measure density at the heel, shin bone, and kneecap

Peripheral dual-energy x-ray absorptiometry (pDEXA)

• This test is a modification of the DEXA technique that measures bone density of limbs like the wrist, heel, or finger
• pDEXA is not appropriate for monitoring BMD after treatment

Single-energy X-ray absorptiometry (SXA)

• Measures the wrist or heel

Dual photon absorptiometry (DPA)

• This test usually has a slower scan time than the other methods but it can measure bone density in the spine, hip, or total body

Single photon absorptiometry (SPA)

• Measures bone density in the wrist

X-ray absorptiometry

• Uses an X-ray of the hand and a small metal wedge to calculate bone density

Peripheral quantitative computed tomography (pQCT)

• A higher radiation method of measuring bone density from bones in limbs, such as the wrist
• Predicts hip, but not vertebral fractures

Vertebral Fracture Assessment (VFA):

• VFA-detected fractures predict future osteoporotic and hip fractures independently of age, weight, and BMD
• It is used for further risk stratification and to aid in clinical decision-making regarding pharmacologic interventions
• It will identify moderate (>25% compression) or severe (>40%) vertebral deformities.
• Unequivocal vertebral fractures (>25% height loss with end-plate disruption) unrelated to trauma are associated with a 5-fold increased risk for recurrent vertebral fractures.
• The advantages of VFA versus standard spine x-rays are convenience, lower cost, and markedly lower radiation exposure

Bone turnover markers (BTMs):

• Measurements of BTMs may provide information about expected rates of bone loss and fracture risk that cannot be obtained from measurements of BMD
• Currently, bone turnover markers cannot be recommended for the prediction of bone loss in individual patients and are not reimbursed by provincial health plans
• Bone formation markers include:
  • Serum osteocalcin
  • Bone-specific alkaline phosphatase (BSAP)
  • C-terminal/N-terminal propeptides of type I collagen (P1CP, P1NP)
• Bone resorption markers include:
  • Urinary hydroxyproline, urinary pyridinoline (PYR)
  • Urinary deoxypyridinoline (D-PYR)
  • Urinary collagen type I cross-linked N-telopeptide (uNTx)
  • Urinary and serum collagen type I cross-linked C-telopeptide (uCTx and sCTx)

Assessment of 10-year risk of fracture with the 2010 tool of the Canadian Association of Radiologists and Osteoporosis Canada (CAROC)

Fracture risk assessment under the CAROC (2010 version) is based upon the femoral neck T-score only

The CAROC tool stratifies women and men over age 50 into three zones of risk for major osteoporotic fracture within 10 years:

• Low (<10%)
  • This group of patients does not need treatment with prescription osteoporosis medications
• Moderate (10-20%)
  • This group of patients requires further assessment to determine whether prescription treatment will be necessary
• High (>20%)
  • This group of patients does require prescription osteoporosis medication regardless of their BMD test results

Risk factors used in CAROC are:

1. Age
2. Sex
3. Hip BMD
4. Steroid use (increases risk level by one category if prednisone daily dose >7.5 mg/day for more than 3 months in the past year)
5. Prior fragility fracture (increases risk level by one category, but hip or vertebral fracture automatically places the patient in the high-risk category)

Assessment of 10-year probability of fracture with the 2011 WHO Fracture Risk Assessment Tool (FRAX) for Canada

WHO Fracture Risk Assessment tool (FRAX) is based upon a more complete set of clinical risk factors that gives immediate calculation of the 10-year probability of a major fracture (clinical spine, wrist, proximal humerus, and hip) or hip fracture alone with or without the addition of bone mineral density (BMD) measured at the femoral neck.

Risk factors used in FRAX are:

1. Age
2. Sex
3. Weight
4. Height
5. Previous fracture
6. Parent fractured hip
7. Current smoking
8. Glucocorticoids
9. Rheumatoid arthritis
10. Secondary osteoporosis
11. Alcohol 3 or more units/day
12. Bone mineral density (BMD) of the femoral neck – (optional)

FRAX Calculation Tool for Canada

Treatment

Clinical Trials

• Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM)
• Risedronate prevents new vertebral fractures in postmenopausal women at high risk

Pipeline Agents

• Odanacatib, New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal women
• A Novel Target for Intervention in the Treatment of Osteoporosis

Physician Resources

1. Tips for patient care

Risk factor management:

• Educate patient about triggers and management
• Discuss primary prevention of fractures
• Diet to maintain normal body weight
• Facilitate smoking cessation
• Reduce or eliminate caffeinated and alcoholic beverages from the diet
• Reduce salt intake
• Encourage recommended calcium and vitamin D intake
• Regular exercise
• Advise and refer to physiotherapists or kinesiologists, to help with the development of appropriate exercise regimen
• Advise use of assistive devices to help with ambulation, balance, lifting and reaching, if required
• Educate to take preventative measures to avoid injury and excessive muscle soreness
• Advise patients to avoid bending forward and exercising with trunk in flexion, especially in combination with twisting

Monitoring:

• Identify individuals with continued BMD loss, despite appropriate osteoporosis treatment
• Repeat BMD assessments after 1-2 years of pharmacologic therapy, or every two-five years in untreated patients,, but recognize that testing more frequently may be warranted in certain clinical situations
• Consider concurrent risk factors and disease states with the prescribed therapy

Medications:

• Advise patient to establish a prescribed routine for pill-taking
• Evaluate risk and benefit ratio of prescribed therapy
• Simplify the dosing regimen where possible
• Selective estrogen receptor modulators (SERM) are contraindicated in women who have a history of thromboembolic events
• Alendronate and risedronate are best taken first thing in the morning with plain a glass of plain water, at least 1/2 hour before eating. The patient recommended staying upright (don’t bend or lie down) for 1/2 hour prior to eating. It is best to avoid using a calcium supplement with breakfast on that day
• Evaluate cost and affordability and insurance coverage when prescribing as this could affect compliance

Social and Stress factors:

• Discuss available therapeutic options and their risk and benefits with the patient
• Counsel patient and family to help lessen the psychological stress, including the potential social embarrassment of having to use a walking aid and other assistive devices

Alerts:

• Fragility fractures are a warning sign of osteoporosis and must be investigated
• Corticosteroid-induced bone loss is believed to be most rapid in the first few months of treatment, especially within the spine
• Selective estrogen receptor modulators (SERM) is contraindicated in women who have a history of thromboembolic events
• Women with breast cancer receiving aromatase inhibitor (AI) therapy may have increased BMD loss and fractures
• Men who receive androgen deprivation therapy (ADT) for prostate cancer are at higher risk for fracture

Activities (physical, mental, others):

• Patients advised to participates in activities of daily living but avoid overwork and fatigue
• Avoid a sedentary lifestyle – encourage regular exercise and structured exercise program
• Mobilize – avoid prolonged sitting/resting

2. Scales and Tables

• When to refer patients for specialized consultation and care
• Institute of Medicine (IOM) Dietary Reference Intakes (DRIs) for calcium
• Institute of Medicine (IOM) Dietary Reference Intakes (DRIs) for vitamin D

References

Core Resources:

• Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist Association. Toronto: Webcom Inc. 2012
• Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2^nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
• Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33^rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
• Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6^th ed. Toronto: Webcom Inc. 2011
• Jeremiah MP, Unwin BK, Greenawald MH, et al. Diagnosis and Management of Osteoporosis. Am Fam Physician 2015;92(4):261-8
• Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11^th ed. New York: McGraw-Hill; 2009
• Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18^th ed. New York: McGraw-Hill; 2011
• McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49^th ed. New York: McGraw-Hill; 2010
• Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9^th ed. St. Louis: Elsevier-Mosby; 2009
• Papaioannou A, Morin S, Cheung AM, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010, 182(17):1864-73
• Papaioannou A, Santesso N, Morin SN, et al. Recommendations for Preventing Fracture in Long-Term Care. CMAJ 2015;187(15):1135-1144. doi: 10.1503/cmaj.141331
• Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9^th ed. St. Louis: Elsevier-Mosby; 2011
• Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24^th ed. St. Louis: Elsevier-Mosby; 2011
• Online resource/weblinks:
  • http://www.merckmanuals.com
  • http://www.osteoporosis.ca
  • http://www.rheuminfo.com

Online Pharmacological Resources:

• e-Therapeutics
• Lexicomp
• RxList
• Epocrates

Journals/Clinical Trials:

• Bono CM, Einhorn TA. Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J. Oct 2003;12 Suppl 2:S90-6
• Bone HG,McClung MR, Roux C et al.Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density. Journal of Bone and Mineral Research. 2010;25: 937-947
• Cadarette SM, Jaglal SB, Kreiger N, et al. Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry. CMAJ 2000; 162:1289
• Cadarette SM, Jaglal SB, Murray TM, et al. Evaluation of decision rules for referring women for bone densitometry by dual-energy x-ray absorptiometry. JAMA 2001; 286:57
• Cooper C, Campion G, Melton LJ 3^rd. Hip fractures in the elderly: a world-wide projection. Osteoporosis Int. Nov 1992;2
• Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med 1995; 332:767
• Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18 2002;359(9319):1761-7
• Eastell R, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. Clin Endocrinol Metab 2019;104(5):1595-1622. doi: 10.1210/jc.2019-00221
• Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int 1997; 7:407.
• Jaglal SB, Weller I, Mamdani M, et al. Population trends in BMD testing, treatment, and hip and wrist fracture rates: are the hip fracture projections wrong?. J Bone Miner Res 2005; 20:898
• Johansson H, Oden A, Johnell O, et al. Optimization of BMD measurements to identify high risk groups for treatment–a test analysis. J Bone Miner Res 2004; 19:906
• Johnell O, Kanis JA, Black DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764
• Johnell O, Kanis, JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006; 17:1726
• Kannus P, Niemi S, Parkkari J, et al. Nationwide decline in incidence of hip fracture. J Bone Miner Res 2006; 21:1836
• Leslie WD, O’Donnell S, Jean S, et al. Trends in hip fracture rates in Canada. JAMA 2009; 302:883
• Lydick E, Cook K, Turpin J, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density. Am J Manag Care 1998; 4:37
• Mauck KF, Cuddihy MT, Atkinson EJ, Melton LJ, 3^rd. Use of clinical prediction rules in detecting osteoporosis in a population-based sample of postmenopausal women. Arch Intern Med 2005;
• Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am. Mar 2003;32(1):39-63
• National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Available at http://www.nof.org/professionals/Clinicians_Guide.htm. Accessed May 5, 2008
• Nymark T, Lauritsen JM, Ovesen O, et al. Decreasing incidence of hip fracture in the Funen County, Denmark. Acta Orthop 2006; 77:109
• Perez-Castrillon JL, Pinacho F, De Luis D et al. Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women Journal of Osteoporosis 2010; 2010), Article ID 401581, 5 pages
  doi:10.4061/2010/401581
• Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. Dec 2005;115(12):3318-25
• Ringe JD, Farahmand P. Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates. Clin Rheumatol. Apr 2007;26(4):474-84
• Rogmark C, Sernbo I, Johnell O, Nilsson JA. Incidence of hip fractures in Malmo, Sweden, 1992-1995. A trend-break. Acta Orthop Scand 1999; 70:19
• Seeman E, Delmas PD. Bone quality–the material and structural basis of bone strength and fragility. N Engl J Med. May 25 2006;354(21):2250-61