Are patients with acromegaly at a higher risk for developing osteoporosis?

Acromegaly and Osteoporosis Risk

Patients with acromegaly have a paradoxically complex bone phenotype: while they may have normal or even increased bone mineral density, they face a significantly increased risk of vertebral fractures, making them susceptible to a form of secondary osteoporosis despite the anabolic effects of growth hormone. 1, 2

The Paradox of Bone Health in Acromegaly

The relationship between acromegaly and bone health is counterintuitive and clinically important:

Fracture Risk is Elevated

• Vertebral fractures occur in approximately 39-40% of acromegalic patients, representing a major complication that persists even after biochemical control is achieved 1, 2
• The increased fracture risk correlates with disease activity and duration, but importantly, fractures continue to occur even after successful normalization of GH and IGF-I levels 1
• These fractures are often mild and asymptomatic but significantly impact quality of life and survival 2

Bone Mineral Density is Often Misleading

• BMD measurements by DXA are frequently normal or even elevated in acromegalic patients, with Z-scores often above expected values 3
• However, BMD is discordant with fracture occurrence - patients fracture despite normal or high BMD 1, 2
• More than 50% of patients have reduced BMD at various skeletal sites, though this doesn't reliably predict fracture risk 2
• A decrease in hip BMD during follow-up has been associated with development of new vertebral fractures, making serial measurements valuable 1

The Mechanism: Bone Quality Over Quantity

• Bone turnover markers are significantly increased in active acromegaly, reflecting high bone remodeling that tends to normalize after biochemical control 1, 4
• The excess GH and IGF-I stimulate both bone formation and resorption, creating increased bone turnover that compromises bone quality despite maintaining or increasing bone mass 2, 5
• Bone quality, rather than bone density, is the critical determinant of fracture risk in acromegaly 2, 4

Contributing Risk Factors

Several factors compound the skeletal fragility:

• Coexistent hypogonadism significantly worsens bone health and must be identified and treated 1
• Diabetes mellitus has additional detrimental effects on bone 1
• Over-replacement with glucocorticoids should be avoided, as supraphysiologic doses further compromise bone health 1
• Male patients appear to have lower Z-scores than females, suggesting gender-specific vulnerability 2

Clinical Screening Recommendations

All patients with acromegaly require screening with thoracic and lumbar spine radiographs at diagnosis and during follow-up, as DXA and QUS methods alone are insufficient for identifying patients at fracture risk 1, 2

The inadequacy of BMD measurements stems from multiple interferences including bone deformities, osteoarthritis, joint rigidity, and soft tissue thickening that are characteristic of acromegaly 2

Management Approach

The cornerstone of preventing skeletal complications includes:

• Achieve biochemical control of acromegaly to normalize bone turnover and reduce ongoing fracture risk 1, 4
• Identify and treat hypogonadism and other modifiable osteoporosis risk factors 1
• Avoid supraphysiologic glucocorticoid doses in patients requiring replacement therapy 1
• Perform serial spine radiographs to detect new vertebral fractures during follow-up 2

Important Caveats

One older study suggested fracture risk might actually be decreased before diagnosis of acromegaly (likely reflecting the anabolic phase), but this protective effect disappears after diagnosis and treatment 3. However, the more recent and higher-quality evidence consistently demonstrates that the clinically relevant issue is the increased vertebral fracture risk that persists despite treatment 1, 2, making this a significant cause of morbidity requiring ongoing surveillance.