Bone Disease

Bone Disease: Screening & Diagnosis

Osteoporosis

  • Postmenopausal women and men age ≥ 50 years with BMD T-score ≤ -2.5 at hip, femur or lumbar spine
  • Premenopausal women and men age < 50 years with BMD Z-score ≤ -2 and fragility fracture

Characteristics

  • Reduced bone mass 
  • Increased incidence of osteoporosis and fractures in PLWH
  • Asymptomatic until fractures occur
  • Aetiology multifactorial
  • Loss of BMD observed with ART initiation (mainly during 1st year)
  • Greater loss of BMD with initiation of certain ARVs(i)

Risk factors

  • Consider classic risk factors(ii) and estimate fracture risk using FRAX in people > 40 years
  • Consider DXA in any person with ≥ 1 risk of(iii):
    1. Postmenopausal women 
    2. Men ≥ 50 years 
    3. High risk for falls(iv)
    4. Those between 40-50 years with high fracture risk (> 20% 10-year major osteoporotic fracture risk based on FRAX assessment without DXA)
    5. History of low impact fracture
    6. Clinical hypogonadism (symptomatic, see Sexual Dysfunction)
    7. Oral glucocorticoid use (minimum 5 mg/d prednisone equivalent for > 3 months) 

Diagnostic tests

  • DXA scan: Preferably perform DXA in those with previous risk factors prior to ART initiation
  • Add DXA result to FRAX® to refine fracture risk prediction (http://www.shef.ac.uk/FRAX)
    - May underestimate risk in PLWH
    - Consider using HIV as a cause of secondary osteoporosis(v)
  • Rule out causes of secondary osteoporosis if BMD low(vi)
  • Lateral spine X-rays (lumbar and thoracic) if low spine BMD, osteoporosis on DXA, or significant height loss or kyphosis develops. (DXAbased vertebral fracture assessment can be used as an alternative to lateral spine X-ray)

Notes:

  1. Greater loss of BMD observed with initiation of regimens containing TDF and some PIs.* Additional loss and gains in BMD observed with switch to and away from TDF-containing ARV regimens, respectively. Clinical relevance to fracture risk not determined. TAF is associated with less bone loss than TDF

    Consider replacing TDF** by non-tenofovir drug or TAF*** if:
    • Osteoporosis / progressive bone loss
    • History of fragility fracture
    • FRAX score for major osteoporotic fracture > 10%

    * There is limited data on use of PIs and changes after their replacement.
    ** Expert opinion, pending clinical data
    *** There is limited data on use of TAF with eGFR ≤ 30 mL/min and longer term outcomes are unknown
  2. Classic risk factors: older age, female gender, hypogonadism, family history of hip fracture, low BMI (≤ 19 kg/m2), vitamin D deficiency, smoking, physical inactivity, history of low trauma fracture, alcohol excess (> 3 units/day), glucocorticoid exposure (minimum prednisone 5 mg/qd or equivalent for > 3 months)
  3. If T-score normal, repeat after 3-5 years in risk groups 1, 2 and 3; no need for re-screening with DXA in risk groups 4 and 5 unless risk factors change and only rescreen group 6 if glucocorticoid use ongoing
  4. Falls Risk Assessment Tool (FRAT), see https://www2.health.vic.gov.au/ageing-and-aged-care/wellbeing-and-participation/healthy-ageing/falls-prevention/falls-prevention-tools
  5. If including BMD within FRAX, entering yes in the secondary cause box will not be considered in the FRAX algorithms, as it is assumed that secondary osteoporosis affects fracture risk solely through BMD
    However, if the contribution of HIV infection to fracture risk is partially independent of BMD, fracture probability may be underestimated by FRAX
  6. Causes of secondary osteoporosis include hyperparathyroidism, vitamin D deficiency, hyperthyroidism, malabsorption, hypogonadism or amenorrhoea, diabetes mellitus, and chronic liver disease

Osteomalacia

Characteristics

  • Defective bone mineralisation
  • Associated with vitamin D deficiency
  • Increased risk of fractures and bone pain
  • Vitamin D deficiency may cause proximal muscle weakness
  • High prevalence (> 80%) of vitamin D insufficiency in some HIV cohorts and in the general population

Risk factors

  • Dark skin
  • Dietary deficiency
  • Avoidance of sun exposure
  • Malabsorption
  • Obesity
  • Renal phosphate wasting(i)

Diagnostic tests

  • Measure 25(OH) vitamin D in all PLWH at presentation. If deficient or insufficient, check PTH levels and consider vitamin D replacement if clinically indicated, see Vitamin D deficiency
  ng/mL nmol/L
Deficiency <10 <25
Insufficiency <20 <50
  • X-rays and bone biopsy can also help in the diagnosis

 Notes:

  1. For diagnosis and management of renal phosphate wasting, see Indications and Tests for Proximal Renal Tubulopathy (PRT)

Osteonecrosis

Characteristics

  • Infarct of epiphyseal plate of long bones resulting in acute bone pain 
  • Rare but increased prevalence in PLWH

Risk factors

  • Low CD4 count
  • Glucocorticoid exposure 
  • IVDU
  • Alcohol
  • Blood coagulation disorders

Diagnostic tests

  • MRI