Osteoporosis in Men

Background

• Osteoporosis in men is an under recognized and undertreated condition that causes significant morbidity and mortality.
• Causes of osteoporosis in men may include primary (related to aging and decreased gonadal function, unassociated with other chronic illness) or secondary (associated with chronic conditions or medications) osteoporosis.
• Potential complications include vertebral or hip fractures.

Evaluation

• Evaluate men at risk for osteoporosis:
  • if > 50 years old and history of fracture (Weak recommendation)
  • if aged 50-69 years and 1 of the following
    • diseases or conditions, such as (Weak recommendation)
      • delayed puberty
      • hypogonadism
      • hyperparathyroidism
      • thyrotoxicosis
      • chronic obstructive pulmonary disease (COPD)
    • uses either glucocorticoids or gonadotropin-releasing hormone agonists (Weak recommendation)
    • lifestyle choices include smoking or alcohol abuse (Weak recommendation)
    • another cause of secondary osteoporosis
  • if ≥ 70 years old (sufficient risk factor for osteoporosis) (Weak recommendation)
• Initial patient evaluation:
  • Obtain detailed history and physical examination to assess for risk factors for osteoporosis and secondary causes of osteoporosis
    • Ask about (including but not limited to)
      • medications and medical conditions that increase risk for osteoporosis
      • falls and/or fractures as an adult
      • parental history of osteoporosis
      • lifestyle factors that increase risk for osteoporosis including, alcohol (≥ 3 drinks daily for men), tobacco use, low calcium intake, and low physical activity level
    • During physical exam
      • assess skeletal deformities which may be a result of unrecognized fractures, such as
        • height loss by comparing current height to maximum adult height
        • kyphosis
      • assess localized vertebral spine tenderness, which may indicate acute vertebral fracture
      • assess balance and mobility
      • determine overall frailty
      • evaluate for signs of secondary causes of osteoporosis , such as
        • COPD
        • consider assessing for testicular atrophy
  • Estimate patient's probability of hip and any major osteoporosis-related fracture using country-specific FRAX (Weak recommendation)
  • Evaluate for secondary causes of osteoporosis:
    • Consider performing blood tests including
      • measuring levels of
        • 25-hydroxyvitamin D (Weak recommendation)
        • calcium (Weak recommendation)
        • creatinine (with estimated glomerular filtration rate) (Weak recommendation)
        • phosphorus (Weak recommendation)
        • parathyroid hormone (PTH) (Weak recommendation)
        • alkaline phosphatase (Weak recommendation)
        • liver transaminases (Weak recommendation)
      • complete blood count (Weak recommendation)
      • total testosterone (Weak recommendation)
    • Consider measuring 24-hour urinary calcium excretion, creatinine, and sodium (Weak recommendation).
    • Consider additional studies in selected patients based on history or physical examination (Weak recommendation).
  • Bone mineral density (BMD) testing
    • Consider BMD based on clinical fracture risk profile and skeletal health assessment, since not everyone has access to BMD.
    • Use dual-energy x ray absorptiometry (DEXA) of spine and hip when measuring BMD (Strong recommendation).
    • If unable to interpret axial skeleton when measuring BMD, use the radius one-third (33%) site is suggested (Weak recommendation).
    • In men receiving androgen-deprivation therapy for prostate cancer or in patients with hyperparathyroidism, consider measuring the one-third (33%) radius site (Weak recommendation).
  • Consider evaluation of bone turnover markers at initial evaluation for osteoporosis; elevated levels are predictive of more rapid rates of bone loss and increased fracture risk (Weak recommendation).
  • Bone biopsy of iliac crest with double tetracycline labeling may be indicated in certain situations.
• Evaluate for prevalent vertebral fractures during initial exam (Strong recommendation)
  • conduct vertebral fracture assessment or lateral spine imaging with standard radiography)
  • if vertebral fracture assessment is unavailable or technically limited, then use lateral spine radiographs (Strong recommendation)

Management

• Lifestyle interventions (diet, physical activity, smoking):
  • For men with or at risk of osteoporosis, recommend calcium intake of 1,000-1,200 mg/day from dietary sources (addition of calcium supplements recommended if dietary calcium insufficient) (Strong recommendation).
  • For men with or at risk for osteoporosis and with low vitamin D levels (< 30 ng/mL [75 nmol/L]), consider offering vitamin D supplementation to achieve blood 25-hydroxyvitamin D (25[OH]D) levels ≥ 30 ng/mL (75 nmol/L) (Weak recommendation).
  • For men at risk of osteoporosis who consume ≥ 3 units/day of alcohol, consider reducing alcohol intake (Weak recommendation).
  • For men at risk of osteoporosis, consider participating in weight-bearing activities for 30-40 minutes per session, 3-4 sessions/week (Weak recommendation).
  • Men at risk of osteoporosis are recommended to cease smoking (Strong recommendation).
• Administer pharmacological therapy to men at high risk of fracture including (Strong recommendation):
  • Men with history of hip or vertebral fracture without major trauma.
  • Men with bone mineral density T-score ≤ -2.5 at spine, femoral neck, and/or total hip.
  • Men in the United States with T-score between -1 and -2.5 in the spine, femoral neck, or total hip plus 10-year risk of any fracture ≥ 20% or 10-year risk of hip fracture ≥ 3% using Fracture Risk Assessment FRAX.
  • Men receiving long-term glucocorticoid therapy of prednisone or equivalent > 7.5 mg/day.
  • Men with prostate cancer receiving androgen-deprivation therapy who have a high risk of fracture.

Table 1. Medication Dosing for Treatment of Osteoporosis in Male Patients

• Selecting pharmacologic therapy:
  • Use a medication approved by regulatory agencies such as FDA or European Union European Medicines Agency, including (Strong recommendation)
    • bisphosphonates (alendronate, risedronate, and zolendronic acid)
    • teriparatide
    • denosumab
  • abaloparatide FDA approved to increase bone mineral density in male patients with osteoporosis at high-risk for fracture or who have failed to respond to or are intolerant to other osteoporosis therapy
  • Medication selections should be individualized based on factors such as (not limited to) (Strong recommendation)
    • fracture history
    • severity of osteoporosis (T-scores)
    • risk of hip fracture
    • patterns of bone mineral density (for example, whether bone mineral density is worse at site were trabecular or cortical bone predominate)
    • comorbid conditions (such as malabsorption conditions, peptic ulcer disease, and gastro esophageal reflux)
  • For men requiring osteoporosis treatment, consider alendronate, risedronate, and zoledronic acid as first-line therapies for fracture prevention (Weak recommendation).
  • For men with a recent hip fracture, consider selecting zoledronic acid (Weak recommendation).
  • If selecting teriparatide, consider not using concomitant antiresorptive therapy (Strong recommendation).
  • Medications not approved in men (such as ibandronate, calcitonin, strontium ranelate) should only be used if approved medications cannot be used (Strong recommendation).
  • For men unable to absorb or tolerate oral agents or oral agents are ineffective, consider other options including zoledronic acid, teriparatide, abaloparatide, and denosumab.
• Follow-up:
  • Bone mineral density testing:
    • Consider testing 1-2 years after initiating medical therapy for osteoporosis (Weak recommendation).
    • If BMD stabilizes, then consider reducing frequency of BMD measurements (Weak recommendation).
  • Consider measuring bone turnover markers 3-6 months after initiating osteoporosis treatment (Weak recommendation).