Available online 28 September 2023, 101824

Author links open overlay panelABSTRACT

Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone health and an increased risk of fracture. However, parameters of bone health that are routinely used to predict fractures in other populations, such as aBMD measured by DXA, are unreliable for this in acromegaly and GHD. Additional methodologies need to be employed to assess bone health in these patients. This review summarizes available data on the effects of acromegaly and GHD on parameters of bone health such as aBMD, volumetric bone mineral density (vBMD) and microarchitecture assessed by HRpQCT and other techniques, trabecular bone score (TBS) and fracture assessment. More research is needed to identify reliable predictors of fracture risk and to determine how best to screen for and treat those patients at risk so that bone health is optimized in these patients.

Section snippetsEFFECTS OF GH AND IGF-1 ON BONE

GH and IGF-1 are important regulators of bone metabolism [1]. GH’s effects on bone are direct as well as via IGF-1. Among their many complex actions, GH stimulates osteoblast cell proliferation and differentiation and IGF-1 stimulates bone resorption, reduces osteoblast apoptosis and promotes osteoblast- and osteoclastogenesis [2], [3]. Systemic IGF-1 may contribute more to cortical bone integrity and locally produced IGF-1 to that of trabecular bone [3]. GH also modulates PTH secretion and

ACROMEGALY

Acromegaly is due in almost all cases to a GH secreting pituitary tumor and characterized biochemically by high levels of GH and IGF-1. Chronic exposure of tissues throughout the body to these hormones in excess results in the multi-system clinical features and co-morbidities characteristic of the disease [4]. Although it was expected that the anabolic effects that physiologic levels of GH and IGF-1 have on the skeleton would preserve bone quality in acromegaly, recent evidence of a high rate

GROWTH HORMONE DEFICIENCY

GHD has complex effects on the skeleton. Age of GHD onset and whether co-existent hypopituitarism are present importantly impact on how and to what extent GHD impairs bone quality. When GHD is prepubertal in onset, skeletal maturation is impaired and short stature ensues [1]. Bone quality appears to be more impaired in adults with childhood onset GHD, as has been reviewed previously[60], [61]. In order to facilitate a comparison to acromegaly, which has its onset post-pubertally, this review

COMPARISON OF BONE HEALTH PARAMETERS IN ACROMEGALY AND GHD

Table 1 summarizes the impact of acromegaly and GHD on parameters of bone health and how acromegaly treatment and GH replacement, respectively, change them. Perhaps most illustrative of the different mechanisms by which these disorders impact on bone is their effects on bone turnover: markers of bone turnover are typically elevated in acromegaly and are lowered with its treatment whereas in GHD these markers are low representing low bone turnover and rise as GH is administered. Although poor

MONITORING OF BONE HEALTH IN ACROMEGALY AND GHD

Bone health has emerged as an important long-term concern for patients with GH excess and deficiency, even those whose GH/IGF-1 levels have been normalized. While it is clear that these patients need monitoring of their bone health, how best to accomplish this in terms of which tests to perform in which patients and at what intervals is not well established. To optimize bone health, both acromegaly and GHD require correction of GH/IGF-1 excess or deficiency. Treatment of hypopituitarism,

SUMMARY

GH and IGF-1 are important regulators of bone metabolism. Both acromegaly, a state of GH and IGF-1 excess, and GHD have detrimental effects on bone health. Markers of bone turnover are high in acromegaly and low in GHD and these are lowered and rise with treatment of each disorder, respectively. aBMD measured by DXA is typically normal in acromegaly and low or normal in GHD. aBMD often improves in GH treatment, but its change with acromegaly treatment is variable. Both disorders have an

Disclosure statement

The author has nothing to disclose.

PRACTICE POINTS

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Markers of bone turnover change in parallel with GH/IGF-1 status in acromegaly and GH deficiency.

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Patients with acromegaly usually have normal aBMD as measured by DXA but are at increased risk for fracture. Acromegaly treatment may not reduce this risk in all patients.

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Adults with GH deficiency may have a low, or in some cases normal, aBMD and have an increased risk of fracture. GH replacement typically increases aBMD and lessens fracture risk of

Funding

Funded by NIH grants DK133392, DK110770.

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