The National Osteoporosis Foundation released an update to its Clinician's Guide to the Prevention and Treatment of Osteoporosis last year (April 2014).

The current version (2014) was released April 1, 2014. The 2014 version of the Clinician’s Guide stresses the importance of screening vertebral imaging to diagnose asymptomatic vertebral fractures; provides updated information on calcium, vitamin D and osteoporosis medications; addresses duration of treatment; and includes an expanded discussion on the utility of biochemical markers of bone turnover and an evaluation of secondary causes of osteoporosis.

Osteoporosis Guidelines

Postmenopausal women and men age 50 and older

National Osteoporosis Foundation (2014) U.S. Preventative Services Task Force among other organizations

Postmenopausal women

American Association of Clinical Endocrinologists (2010) – North American Menopause Society (2010)

Men

Endocrine Society (2012)

Review of the 2014 NOF Clinician's Guide

Approach to the diagnosis and management of osteoporosis
Universal Recommendations
Pharmacotherapy (Who) and FDA indications
Sequential and combination therapy
Duration of treatment

Dual‐energy Absorptiometry (DXA) Bone Density Testing: Indications

NOF guideline
- Women > 65 years old and men > 70 years old
- Younger postmenopausal women, women in the menopausal transition, and men age 50‐69 years old with clinical risk factors for fracture • e.g., current smoker, low body weight, history of osteoporosis, low trauma fracture in a first‐degree relative
- Adults who have a fracture after age 50 years
- Adults with specific conditions or medications associated with bone loss
Other – Women 50‐ 64 years old with FRAX overall fracture risk > 9.3% (USPSTF) –

WHO Definition of Osteoporosis Based on Bone Mineral Density testing results:

Normal
- BMD within 1 SD of the mean level for a young-adult reference population
- T-score at -1.0 and above
Lone Bone Mass (Osteopenia)
- BMD between 1.0 and 2.5 SD below that of the mean level for a young-adult reference population
- T-score between -1.0 and -2.5
Osteoporosis
- BMD 2.5 SD or more below that of the mean level for a young adult reference population
- T-score at or below -2.5
Severe or Established Osteoporosis
- BMD 2.5 SD or more below that of the mean level for a young adult reference population
- T-score at or below -2.5 with one or more fractures

Imaging Recommendations

Vertebral Imaging recommended for women age 70 and older and all men age 80 and older if BMD T-score at the spine, total hip or femoral neck is </= -1.0
Women age 65-69 and men age 70-79 if BMD T-score at the spine, total hip or femoral neck is </= -1.5
Postmenopausal women and men age 50 and older with specific risk factors: low trauma fracture during adulthood (age 50), historical height loss of 1.5 inches or more (4 cm), prospective height loss of 0.8 inches or more (2 cm), or recent or ongoing long-term glucocorticoid treatment.

FRAX was developed to calculate a 10-year probability of a hip fracture and the 10-year probability of a major osteoporotic fracture (defined as clinical vertebral, hip, forearm or proximal humerus fracture). FRAX algorithm available at www.nof.org as well as at www.shef.ac.uk/FRAX.

FRAX is for postmenopausal women and men age 50 and older. In patients being pharmacologically treated for osteoporosis, clinical judgment must be use in interpreting results. No treatment in 2 years could be interpreted as untreated. Femoral neck BMD is preferred in calculating FRAX.

Diagnosis of Osteoporosis (WHO Criteria) (Postmenopausal women and men >/= 50 years of age)

T‐score at ‐1.0 or above (SD) Normal
T‐score between ‐1.0 and ‐2.5 (SD) - Low bone mass (Osteopenia)
T‐score at or below ‐2.5 (SD) - Osteoporosis
T‐score at or below ‐2.5 (SD) with one or more fractures - Severe or established osteoporosis SD = standard deviation

Diagnosis of Osteoporosis (International Society for Clinical Densitometry 2007 Guidelines)*

Z‐score above ‐2.0 (SD) “Within the expected range for age”
Z‐score at or below ‐2.0 (SD) “Low bone mineral density for chronological age” or “Below the expected range for age” SD = standard deviation Premenopausal Women, Men < 50 Years of Age, and Children * These criteria are never used alone to diagnose osteoporosis in these populations

RECOMMENDATIONS IN ALL PATIENTS:

Several interventions to preserve bone strength can be recommended to the general population. These include an adequate intake of calcium and vitamin D, lifelong participation in regular weight-bearing and muscle-strengthening exercise, cessation of tobacco use, identification and treatment of alcoholism, and treatment of risk factors for falling.

Bone‐Healthy Lifestyle:

Calcium - Recommended elemental calcium intake should be obtained ideally through dietary sources + supplements
Age Group Recommended Daily Intake Maximum Daily Intake
- 19-50 years 1000 mg
- 50-70 years 2000 mg Men = 1000 mg Women = 1200 mg
- ≥ 71 years 1200 mg

According to the updated 2014 National Osteoporosis Foundation guideline, intakes of calcium in excess of 1200 to 1500 mg per day could place a patient at increased risk for kidney stones, cardiovascular disease (CVD), and stroke. (J Bone Metab 2014;29:531‐3; J Bone Metab 2014;21:21‐8; Am J Clin Nutr 2011;94:270‐277)

Vitamin D: This is the amount needed to maintain the majority of healthy patients within the sufficient range

Age Group Recommended Daily Intake
- National Osteoporosis Foundation (2014)
  - <50 years 400-800 units (4000 units max daily intake)
  - ≥ 50 years 800-1000 units (4000 units max daily intake)
Institute of Medicine (2010)
- ≥ 71 years 800 units (4000 units max daily intake)
- 51-70 years 600 units (4000 units max daily intake)
- 19-50 years 600 units (4000 units max daily intake)

When to Consider Drug Treatment

History of (low trauma) hip or vertebral fracture
T‐score - ‐2.5 at femoral neck, hip, or spine by central DXA
Postmenopausal women and men 50 years of age if T‐score between –1 and –2.5 and 10‐year hip fracture probability of 3% or a 10‐year all major osteoporosis‐related fracture probability of 20%

Bisphosphonates: inhibit osteoclastic bone resorption and reduce osteoclast activity and beneficial effect on osteoblasts.

Drug holidays are being considered for bisphosphonates to prevent which serious long‐term adverse effects
Show residual effects after discontuation
Evidence for efficacy beyond 5 years is limited, whereas rare safety concerns become more common beyond 5 years.
Reasonable to discontinue after 3-5 years in patients who have a modest risk of fracture after the initial treatment period, but in high risk, continued treatment or alternative treatment should be considered.

Non-Bisphosphonates: produce temporary effects that wane with discontinuation.

Duration of Treatment and Drug Holiday

Alendronate: Duration of treatment 5 years. Assessment for reinitiation: 1-2 years
Risedronate: Duration of treatment 5 years. Assessment for reinitiation: 1 year
Zoledronic acid: Duration of treatment 3 years. Assessment for reinitiation: 2-3 years

Denosumab Role in Therapy

FDA osteoporosis indications
- Postmenopausal women and men with high fracture risk (Osteoporosis fracture, multiple risk factors, can’t use other meds)
- Androgen deprivation therapy for nonmetastatic prostate cancer
- Adjuvant aromatase inhibitor for breast cancer
AACE guideline – first line
Increases BMD for at least 8 years
Vertebral, hip, & nonvertebral fracture prevention
Quicker reversal with medication discontinuation
Adverse effects: Common adverse reactions (> 5% and diff placebo)
- Back, shoulder, leg, and musculoskeletal pain – Increased cholesterol – Cystitis
- Cases of MRONJ and atypical fractures

Raloxifene Role in Therapy

FDA indications
- Osteoporosis prevention and treatment
- Postmenopausal women with osteoporosis and/or at high risk for invasive breast cancer
AACE guideline –Second‐ and third‐line therapy
Dose ‐ 60 mg daily
Contraindications ‐ active or past history venous thromboembolism
Precaution – risk for stroke
Adverse effects – Vasomotor symptoms (hot flushes) – Leg cramps – Breast tenderness – Spotting – Venous thromboembolism – Box warning – fatal stroke

Teriparatide Role in Therapy

FDA indications
- Postmenopausal women at high risk for fracture
- Men with primary or hypogonadal osteoporosis at high risk for fracture
- Glucocorticoid‐induced osteoporosis
- High fracture risk
  - Previous fracture
  - Extremely low BMD (T‐score < ‐3.5)
  - Multiple risk factors for fracture
- Teriparatide Dose, Selection, and Common Adverse Effects
  - 20 mcg subcutaneously daily for 24 months
  - Once weekly injection in trials – ? Start antiresorptive agent before end of therapy
  - Contraindications – Skeletal muscle radiation, bone cancer, hypercalcemia, Paget’s disease
  - Common adverse effects
    - Orthostasis – first doses
    - Nausea, arthralgia, leg cramps
    - Hypercalcemia (check calcium at baseline)
    - Box warning ‐ osteosarcoma (animal data)

Calcitonin: Role in Therapy, Efficacy, Dose, and Adverse Effects

FDA indication – osteoporosis treatment for women 5 years post menopause with low bone mass
AACE guideline – fourth‐line therapy
Only vertebral fracture prevention
Dosing –Intranasal ‐ 200 units daily alternating nares
Adverse effects –Nasal – rhinitis, epistaxis, irritation –Subcutaneous – pain, redness –Other – nausea, allergic response, backache, headache –FDA post‐marketing analysis for cancer risk

References:

National Osteoporosis Foundation (2014)
U.S. Preventive Services Task Force – calcium vitamin D (2013)
Ann Intern Med 2013;158:691‐696
U.S. Preventive Services Task Force – screening (2011) – www.uspreventiveservicestaskforce.org/uspstf/uspsoste.htm
International Society for Clinical Densitometry (2013) – www.iscd.org/documents/2013/07/2013‐iscd‐official‐ positions‐adult.pdf
American Association of Clinical Endocrinologists(2010)
Endocr Pract 2010;16(Suppl 3):1‐37
North American Menopause Society (2010) – www.menopause.org/docs/default‐document‐ library/psosteo10.pdf?sfvrsn=2
Endocrine Society (2012) – J Clin Endocrinol Metab 2012;97:1802‐1822

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