Guideline sources The following summarized guidelines for the evaluation and management of osteoporosis are prepared by our editorial team based on guidelines from the American College of Physicians (ACP 2023), the U.S. Preventive Services Task Force (USPSTF 2018), the American College of Endocrinology (ACE/AACE 2016), and the Osteoporosis Canada Foundation (OC 2010; 2006). 1 2 3 4 5 6 7 7 7 8 9 10 11 Definition Osteoporosis is a skeletal disease associated with a reduction in bone density, which predisposes to an increased risk of bone fractures. 7 Epidemiology https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 1/10 6/30/23, 1:24 AM p Osteoporosis Pathway gy Postmenopausal osteoporosis is caused by estrogen deficiency in women. Causes of secondary osteoporosis include endocrine disorders (e.g. hyperthyroidism, hyperparathyroidism), malabsorption disorders (e.g. celiac disease, IBD), autoimmune disorders (e.g. ankylosing spondylitis), CKD, as well as medications (e.g. glucocorticoids). 7 10 Pathophysiology In the United States, the prevalence of osteoporosis in women >50 years of age ranges from 10% to 17%. The overall prevalence of osteoporosis in the United States is estimated at 10.3%. 8 9 Disease course In patients with osteoporosis, a progressive decrease in trabecular bone width and cortical bone thickness occurs due to increased bone resorption and decreased bone formation. These structural alterations in bone predisposes to fractures and associated morbidity. 7 Prognosis and risk of recurrence Osteoporotic fractures are associated with an increased risk of mortality, which persists for 5 years for all fractures and up to 10 years after a hip fracture. Predictors of mortality after fragility fracture include age, quadriceps weakness, and subsequent fractures. 11 Guidelines 1. Screening and diagnosis Indications for screening: As per USPSTF 2018 guidelines, screen for osteoporosis in women 65 years of age, and in women whose fracture risk is greater than or equal to that of a white woman without additional risk factors at 65 years of age. B As per OC 2010 guidelines, assess all patients > 50 years of age who have experienced a fragility fracture for osteoporosis and fracture risk. A 2. Classification and risk stratification Risk stratification: assess the absolute risk of fracture based on established factors, including age, bone mineral density, prior fragility fractures and corticosteroid use. A 3. Diagnostic investigations Clinical history: As per OC 2010 guidelines: Obtain a detailed history identify risk factors for low bone mineral density, falls and fractures: https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 2/10 6/30/23, 1:24 AM Osteoporosis Pathway prior fragility fractures parental hip fractures corticosteroid use current smoking high alcohol intake 2 rheumatoid arthritis. Assess for a history of falls in the past year. Conduct a multifactorial risk assessment, including the ability to get out of a chair without using arms, in patients without a history of falls. A Physical examination: As per OC 2010 guidelines: Measure height annually, and assess for the presence of vertebral fractures on physical examination. A Perform a focused physical examination to identify undiagnosed vertebral fractures, as follows: measure weight (weight loss > 10% since age 25 is significant) measure height annually (prospective loss > 2 cm is significant or historical height loss > 7 cm) measure rib to pelvis distance (< 3 fingers' breadth is significant) measure occiput-to-wall distance for kyphosis (> 5 cm is significant). Initial laboratory tests: Obtain the following laboratory investigations as part of the initial evaluation of patients with osteoporosis: calcium (corrected for albumin) CBC creatinine ALP TSH SPEP in case of vertebral fracture 25-hydroxyvitamin D. Vitamin D levels: As per OC 2010 guidelines: Measure serum 25-hydroxyvitamin D levels in patients: who will receive pharmacologic therapy for osteoporosis who have sustained recurrent fractures or have bone loss despite osteoporosis who have comorbid conditions that affect absorption or action of vitamin D. B Measure serum 25-hydroxyvitamin D levels after 3-4 of adequate supplementation, and do not repeat measurement if an optimal level ( 75 nmol/L) is achieved. B Bone mineral density testing: https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 3/10 6/30/23, 1:24 AM Osteoporosis Pathway As per OC 2010 guidelines: Obtain bone mineral density testing in younger adults (< 50 years of age) with one of the following: fragility fracture prolonged use of corticosteroids use of other high-risk medications (e.g. aromatase inhibitors, androgen deprivation therapy) hypogonadism or premature menopause (< 45 years of age) primary hyperparathyroidism other disorders strongly associated with rapid bone loss and/or fracture. Obtain bone mineral density testing in older adults ( 50 years of age) with one of the following: fragility fracture prolonged use of corticosteroids (at least 3 months of prednisone equivalent dose of 7.5 mg PO DIE) parental hip fracture vertebral fracture or osteopenia on radiography current smoking high alcohol intake low body weight (< 60 kg) or major weight loss (> 10% of body weight at 25 years of age) rheumatoid arthritis other disorders strongly associated with osteoporosis. T- and L- spine radiography: obtain lateral thoracic and lumbar spine XRs, or vertebral fracture assessment by DEXA, if clinical evidence is suggestive of a vertebral fracture. A Evaluation for secondary causes: as per OC 2010 guidelines, obtain additional biochemical testing to rule out secondary causes of osteoporosis in selected patients, on the basis of the clinical assessment. B 4. Medical management Indications for antiresorptive treatment: offer pharmacologic therapy to patients > 50 years of age who have had a fragility fracture of the hip or vertebra. B Show 3 more Landmark trials: Alendronate for osteoporosis in men In male patients with osteoporosis, alendronate was superior to placebo with respect to gain in bone mineral density at the lumbar spine at 2 years. Orwoll E et al. N Engl J Med. 2000 Aug 31. https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 4/10 6/30/23, 1:24 AM Osteoporosis Pathway Initial antiresorptive therapy: As per ACP 2023 guidelines, initiate bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal patients with primary osteoporosis. A Show 4 more As per OC 2010 guidelines, initiate alendronate, risedronate, zoledronic acid, or denosumab as first-line therapy for the prevention of fractures in menopausal females requiring treatment for osteoporosis. A Show 2 more Recombinant PTH and PTH-related protein analogs: consider using teriparatide only in patients with severe osteoporosis, defined as > 1 fragility fracture and very low bone mineral density. C Show 2 more Hormone therapy: Use hormone therapy as first-line therapy to prevent hip, nonvertebral and vertebral fractures in menopausal women requiring treatment of osteoporosis in combination with treatment for vasomotor symptoms. A Avoid using testosterone for the treatment of osteoporosis in men. D Calcitonin and etidronate: consider calcitonin or etidronate to prevent vertebral fractures in menopausal women who are intolerant of first-line therapies. C Combination antiresorptive therapy: avoid simultaneously prescribing multiple antiresorptive agent for fracture risk reduction. D Duration of treatment: maintain osteoporosis therapy without a drug holiday in individuals at high risk for fracture. B 5. Nonpharmacologic interventions Calcium supplementation: as per OC 2010 guidelines, aim for a total daily intake of 1,200 mg of elemental calcium (through diet and supplements) in individuals over age 50. B Vitamin D supplementation: As per OC 2010 guidelines: Advise routine daily supplementation of 400-1,000 IU (10-25 g) of vitamin D3 in healthy adults at low risk of vitamin D deficiency. B Advise daily supplementation of 800-1,000 IU (20-25 g) of vitamin D3 daily in > 50 years old adults at moderate risk of vitamin D deficiency. Recognize that > 1,000 IU (25 g) daily supplementation may be required to achieve optimal vitamin D status. Recognize that daily doses of up to 2,000 IU (50 g) are safe and do not necessitate monitoring. B 6. Surgical interventions https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 5/10 6/30/23, 1:24 AM Osteoporosis Pathway Vertebroplasty and kyphoplasty: avoid performing vertebroplasty and kyphoplasty as first-line treatment of vertebral fractures, given the unclear benefit on overall pain, and the potential increased risk of vertebral fractures in adjacent vertebrae. D 7. Specific circumstances Patients on corticosteroids: initiate a bisphosphonate at the outset and continue for at least the duration of the corticosteroid therapy, for patients over 50 years of age who are on long-term corticosteroid therapy. A Show 2 more Patients on aromatase inhibitors: assess women who are taking aromatase inhibitors for fracture risk, and consider osteoporosis therapy to prevent fractures. B Patients on androgen-deprivation therapy: assess men who are undergoing androgen- deprivation therapy for fracture risk, and consider osteoporosis therapy to prevent fractures. B 8. Patient education General principles: implement an educational initiative targeting both the patient and the primary care physician following a fragility fracture. B Risks and benefits of treatment: discuss the potential benefits and risks of pharmacological agents with patients before initiation of therapy, in order to support informed decision-making. B 9. Preventative measures Calcium and vitamin D supplementation: insufficient evidence to assess the balance of benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in males and premenopausal females. I Show 3 more Prevention of falls: As per OC 2010 guidelines: Consider offering exercises focusing on balance, such as tai chi, or on balance and gait training in individuals at risk of falls. B Consider offering hip protectors in older adult patients at high risk for fracture residing in long- term care facilities. C 10. Follow-up and surveillance Indications for specialist referral: Refer patients to a specialist in the following clinical scenarios: when a patient with normal BMD sustains a fracture without major trauma B https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 6/10 6/30/23, 1:24 AM Osteoporosis Pathway when recurrent fractures or continued bone loss occurs in a patient receiving therapy without obvious treatable causes of bone loss B when osteoporosis is unexpectedly severe, has unusual features, or less common secondary conditions are identified, such as hyperthyroidism, hyperparathyroidism, hypercalciuria, or elevated prolactin B when a patient has a condition that complicates management, such as CKD with a GFR < 35, hyperparathyroidism, or malabsorption B Assessment of treatment response: as per AACE 2016 guidelines, successful treatment of osteoporosis is defined as stable or increasing BMD with no evidence of new fractures or fracture progression. A Monitoring of treatment response: as per AACE 2016 guidelines, obtain a baseline axial (spine and hip) DXA, and repeat DXA every 1 to 2 years until findings are stable. Continue with follow-up DXA every 1 to 2 years or at a less-frequent interval, depending on clinical circumstances. B Show 3 more Clinical findings Patient demographics Symptoms Asian ethnicity Acute back pain Elderly age Loss of height Female sex Past obstetric history Past medical history Postmenopause Cancer Family history Celiac disease Corticosteroid use Osteoporosis Crohn's disease Musculoskeletal exam Eating disorder Fragility fracture Stooped posture Hyperthyroidism femoral neck T-score IBD height Kidney failure Multiple myeloma Imaging findings Rheumatoid arthritis lumbar spine T-score SLE mid-third radius T-score Past surgical history total hip T-score Gastrointestinal surgery Social history Alcohol consumption https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 7/10 6/30/23, 1:24 AM Osteoporosis Pathway Current cigarette smoking Lab findings serum PTH serum calcium serum estrogen serum testosterone Likelihood Ratios Pertinent positives The following findings increase the probability of osteoporosis in women. 11 12 Finding LR+ Value Decreased weight (< 51 kg) 7.3 (5.0-10.8) Increased wall to occiput distance (> 0 cm) 4.6 (2.9-7.3) Decreased rib to pelvis distance (< 2 fingers' breadth) 3.8 (2.9-5.1) Decreased tooth count (< 20) 3.4 (1.4-8.0) Show 2 more Pertinent positives The following findings increase the probability of osteoporosis in men. 12 Finding LR+ Value Decreased osteoporosis self-assessment tool (OST) ( 3) 2.4 (2.0-2.9) Pertinent negatives The following findings decrease the probability of osteoporosis in women. 12 Finding LR- Value osteoporosis risk assessment instrument (ORAI) not increased (< 9 points) 0.13 (0.04-0.40) Pertinent negatives The following findings decrease the probability of osteoporosis in men. 12 Finding LR- Value osteoporosis self-assessment tool (OST) not decreased (> 3) 0.35 (0.23-0.53) Studies https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 8/10 6/30/23, 1:24 AM Osteoporosis Pathway 2000 Alendronate for osteoporosis in men In male patients with osteoporosis, alendronate was superior to placebo with respect to gain in bone mineral density at the lumbar spine at 2 years. Orwoll E et al. N Engl J Med. 2000 Aug 31. References 1. Papaioannou A, Morin S, Cheung AM et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010 Nov 23;182 17 1864 73. Open 2. Amir Qaseem, Lauri A Hicks, Itziar Etxeandia-Ikobaltzeta et al. Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. Ann Intern Med. 2023 Jan 3. Online ahead of print. Open 3. US Preventive Services Task Force, David C Grossman, Susan J Curry et al. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Apr 17;319 15 1592 1599. Open 4. Camacho PM, Petak SM, Binkley N et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guideline for the Diagnosis and Treatment of Postmenopausal Osteoporosis 2016. Endocr Pract. 2016 Sep 2;22 Suppl 4 1 42. Open 5. US Preventive Services Task Force, Curry SJ, Krist AH et al. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Jun 26;319 24 2521 2531. Open 6. Anthony Hodsman, Alexandra Papaioannou, and Ann Cranney. Clinical practice guidelines for the use of parathyroid hormone in the treatment of osteoporosis. CMAJ. 2006 Jul 4; 175 1 48. Open 7. Franic D, Verdenik I. Risk Factors for Osteoporosis in Postmenopausal Women - from The Point of View of Primary Care Gynecologist. Zdr Varst. 2018 Jan 5;57 1 33 38. Open 8. Skrzat J, Brzegowy P, Tarasiuk J et al. Comparison of volumetric reconstructions obtained from CT and micro-CT scans of the petrous bone. Folia Med Cracov. 2016;56 4 63 70. Open 9. Wright NC, Looker AC, Saag KG et al. 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. J Bone Miner Res. 2014 Nov;29 11 2520 6. Open 10. Faryal Mirza, Ernesto Canalis. Management of endocrine disease: Secondary osteoporosis: pathophysiology and management. 2015 Sep;173 3 R131 51.2015 Sep;173 3 R131 51. Open 11. Dana Bliuc, Nguyen D Nguyen, Vivienne E Milch et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. 2009 Feb 4;301 5 513 21.2009 Feb 4;301 5 513 21. Open 12. Amanda D Green, Cathleen S Col n-Emeric, Lori Bastian et al. Does this woman have osteoporosis?. JAMA. 2004 Dec 15;292 23 2890 900. Open 13. Simel D, Rennie D. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. Mayo Clin Proc. 2009 Nov; 84 11 1045. Open https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 9/10 6/30/23, 1:24 AM Osteoporosis Pathway 14. Moyer VA. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 May 7;158 9 691 6. Open 15. Eastell R, Rosen CJ, Black DM et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1;104 5 1595 1622. Open 16. Malabanan AO, Rosen HN, Vokes TJ et al. Indications of DXA in women younger than 65 yr and men younger than 70 yr: the 2013 Official Positions. J Clin Densitom. 2013 Oct-Dec;16 4 467 71. Open 17. Dolores Shoback, Clifford J Rosen, Dennis M Black et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105 3):dgaa048. Open 18. Expert Panel on Musculoskeletal Imaging, Joseph S Yu, Nidhi G Krishna et al. ACR Appropriateness Criteria Osteoporosis and Bone Mineral Density: 2022 Update. J Am Coll Radiol. 2022 Nov;19 11S S417 S432. Open 19. Charles L Shapiro, Catherine Van Poznak, Christina Lacchetti et al. Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline. J Clin Oncol. 2019 Nov 1;37 31 2916 2946. Open https://web.pathway.md/diseases/rec5pLkqSMfomNMpD 10/10