The result showed that exposure to growth hormone was able to stimulate OPG secretion in a concentration-dependent GH [ 12 ]. Ueland et al. It was obvious that gonadal status did not affect the turnover parameters. Positive correlation between osteocalcin and CTx was observed in both genders, suggesting that bone turnover is synchronized. Coupling phenomenon was more discussed in studies with adult GH deficiency [ 13 , 14 ], and it is defined as bone remodeling initiated by osteoclastic resorption, which is under physiological conditions temporarily followed by osteoblastic bone formation.
Positive effect of GH on bone formation was confirmed by De Paula et al. In our study with 94 growth hormone deficient adults [ 15 ] we have observed carboxy-terminal collagen crosslinks CTX , marker of bone resorption, and it was increasing during first year of GH replacement treatment.
After one year of treatment period CTX was slightly decreasing for 2 years. On the opposite site, levels of osteocalcin, marker of bone formation, were significantly rising during whole 2-year treatment period. This study demonstrated positive effect of GH on bone markers with predominance to bone formation. According to this study we could suppose that possible analogy exists with active acromegaly. Parkinson et al. Pegvisomant induced normalization of serum IGF-1, which was associated with a significant decreased markers of bone formation and resorption.
After normalization of IGF-1 there was no statistically significant difference between patients and controls for all parameters of bone turnover. In contrast to other studies, this study has not observed significant correlation between osteocalcin and serum GH or IGF-1, probably due to small size of study cohorts.
A significant positive correlation between GH and osteocalcin was observed in study of Piovesan et al. This study also demonstrated that patients with active acromegaly have increased levels of osteocalcin and PIIINP as the reflect of increased osteoblastic activity.
To summarize, active acromegaly leads to increase in bone turnover markers. Studies have proven correlation between bone resorption and formation, suggesting coupling between bone turnover markers. After treatment with somatostatin analogues pegvisomant and octreotide bone markers and IGF-I normalize.
Study of transsphenoidal surgery effect on bone turnover is missing. The whole effect of growth hormone excess on bone mineral density is not fully explained. It was confirmed that BMD of lumbar spine and femoral neck was increased by patients with active acromegaly. Most studies suggest that cortical bone mass is increased in acromegaly, whereas trabecular bone seems largely unaffected, confirming that the actions of GH are mediated also by local produced IGFs [ 19 ].
Recently, studies have proven lower BMD even osteoporosis in patients with active and controlled acromegaly. Madiera et al. There was no difference in Z -score and T -score between groups with active or controlled acromegaly. Giuseppina et al. Study by Madiera et al. Higher T -score was observed in eugonadal patients with active acromegaly compared to controlled hypogonadal patients and the most of osteoporotic patients were hypogonadal.
The effect of gonadal status on BMD in acromegalic patients is ambiguous. Some studies [ 20 , 21 ] have proven positive effect of eugonadism on bone mineral density, but some studies [ 22 , 23 ] have shown controversial results, higher bone mineral density regardless of gonadal status. The most affected measured site was distal radius because the results of BMD of femur or lumbar spine could be distorted by periarticular calcifications and cartilage damage, which is very common in acromegaly [ 24 ].
Association between gonadal status and bone mineral density was found by univariate testing, but multivariate analysis has confirmed the importance of age and gender. Age and gender could by defined as main determinants of bone remodelation mechanisms, indicating that the same process influences bone loss in normal population, growth-hormone-deficient adults and also in acromegalic patients [ 7 ].
According to published discrepancies between studies concerning BMD in acromegalic patients, BMD seems to be not a proper marker for fracture risk assessment. Adequately designed studies focusing on quality of bone in patient with acromegaly are missing, and new methods for bone quality assessment explaining fracture risk are required. According to existing criteria of osteoporosis risk it is not possible to asses exact risk of fracture, similarly as it was described in patients suffering from diabetes mellitus type II.
It was described that cortical bone in acromegaly changes in opposite to trabecular bone. Results of few past studies remain controversial. Recent studies suggest that BMD decreases in patients with active controlled disease. As it was described in previous text influence of gonadal status plays also the role in bone mass acquisition, proving that hypogonadal patients with controlled disease have higher prevalence of osteoporosis in comparison to eugonadal noncontrolled acromegalic patients.
According to gonadal status also gender difference was described in acromegalic patients, supported by studies with GH deficient patients treated with recombinant human growth hormone. Less discussed, but very important, was BMD measurement technique in past studies. It suggested that two-dimensional DXA is distorted because it is not counting with perpendicular scan bone density. Thus, other techniques should be used for assessment of BMD. At last, the clinical access to acromegalic patient should be individual with emphasis to state of disease, gonadal status, gender, age, measured site of bone measuring technique.
Only in one study [ 25 ] increased prevalence of radiological vertebral fractures in postmenopausal women with acromegaly was observed. It is unknown whether increased fracture risk is a result of different risk factors in this population. As it was mentioned, acromegaly is traditionally considered as a cause of secondary osteoporosis, but BMD is not decreased and its measurement is overestimated because of structural modification of spine.
In another studies, it was shown that GH excess has effect on trabecular bone but no effect on cortical bone [ 4 , 26 ]. Lower bone mass of trabecular bone could be influenced by many factors, but the most probable seems to be hypogonadism.
Circulating sex hormones have better affinity to trabecular bone and in spite of sex hormones low levels in this group of patients are able to affect trabecular bone. Interesting finding was published in recent study of Giuseppina et al.
Based on these findings an insufficient quality of bone should be the most important factor of bone health, and it is influenced by gonadal status, disease activity, and gender. Full-understanding of the problematic of osteoporotic fractures in patients with acromegaly requires other studies with higher number of patients. The articular manifestations of acromegaly are one of the most frequent clinical complications and may be present as the earliest symptom of acromegaly.
Its prevalence and severity worsen with the duration of uncontrolled disease and often result in significant disability. The pathogenesis of arthropathy in acromegaly is comprised of two mechanisms: initial endocrine and subsequent mechanical changes [ 27 ].
Radiological changes in this early phase are joint space widening and periarticular soft tissue hypertrophy.
With ongoing disease arthropathy becomes irreversible and biochemical control of acromegaly, as documented by a normal IGF-I, will have a very small efficacy in improving the clinical status. Altered joint geometry results in repeated intraarticular trauma and exaggerated a reparative reaction which leads to scar, cysts, and osteophyte formation with further worsening of joint geometry. At this point, the disease acquires the characteristics and features of degenerative joint disease [ 28 ].
Radiographic changes at this stage are characterized by narrowing of joint spaces see Figure 2 , osteophytosis, cysts, and other features typical for the later stages of the disease see Table 1 [ 29 ]. The radiological appearance of arthropathy in acromegaly was mostly studied in small noncontrolled groups of patients with untreated and treated but active disease.
These studies have suggested that more severe radiological abnormalities were related to biochemically more active acromegaly and longer disease duration [ 30 ]. Further common complaints relate to limited range of movement, joint instability, and joint deformation. The presence of radiologic abnormalities and clinical manifestations of arthropathy are not correlated, unless joints are severely affected as in long-standing disease [ 28 ].
There were few studies evaluating prevalence of joint changes in acromegalic patients. Recent study evaluated 89 acromegalic patients with adequate long-term disease control for prevalence and radiological characteristics of arthropathy.
They found evidence for radiological arthritis in a least one joint in all patients and clinical arthritis in two-thirds of patients. The most prevalent manifestation was axial osteoarthritis, affecting the cervical and lumbar areas, even at young ages.
The characteristic radiological changes observed were wide joint spaces and severe osteophytosis [ 3 ]. In early phase of the disease widened intervertebral spaces and vertebral enlargement may be present in the spine X-ray. Ossification of the anterior surface of vertebral bodies is relatively common and in more severe cases can bridge the disc space resembling diffuse idiopathic skeletal hyperostosis syndrome.
Biermasz et al. These joint problems were an important indicator of impaired quality of life. Osteoarticular manifestations of acromegaly are the most frequent clinical complications and may be present as the earliest symptom in a significant proportion of patients with acromegaly. Many patients with joint complaints are misdiagnosed as a generalized osteoarthritis. Early diagnosis of acromegalic arthropathy and aiming the therapy could lead to decrease in severe joint complications, a disability.
This effect is proved by high levels of bone turnover markers in active acromegaly, and correlation between IGF-I and bone remodeling was proven by few past studies. Nowadays, it is frequently discussed if BMD as predictor of osteoporotic fractures in patient with acromegaly is unchanged according to earlier studies or decreased according to few recent studies.
It was shown that GH excess has effect on trabecular bone but no effect on cortical bone, thus quality of bone remains to be more important in osteoporotic fracture risk, but another studies are needed. Supposed increased fracture risk cannot be fully explained by changes in bone mineral density. It seems that bone quality plays the most important role in fracture risk regardless of BMD.
Nowadays, in clinical practice noninvasive methods to asses bone quality are missing. Adequately designed studies focusing on different parameters of bone quality in patient with acromegaly are required. Assessment of patient risk profile could be helpful in stratification of patients with high risk of fracture. In clinical practice beside BMD testing and bone turnover evaluation fracture risk assessment using FRAX calculator could be helpful in fracture risk prediction. Prevalence and severity of arthropathy worsen with the duration of uncontrolled disease and often result in significant disability.
Here, we report a year-old Japanese woman with acromegaly, who complained of bilateral finger stiffness and polyarthralgia two months after transsphenoidal surgery of a growth hormone GH -secreting pituitary adenoma. Postoperative levels of serum GH and insulin-like growth factor-1 IGF-1 were markedly decreased without any secretory deficiency of other anterior pituitary hormones.
Hand X-ray did not show typical RA changes; however, erosive changes in carpal bones were clearly detected by magnetic resonance imaging with gadolinium enhancement. Has chiropractic or acupuncture treatment been explored? I have found chiropractic treatment helpful for spinal problems.
Save my name, email, and website in this browser for the next time I comment. Pituitary World News. Home Acromegaly Arthritis and acromegaly. Acromegaly Dr Blevins Corner Podcasts. Like this: Like Loading Acromegaly: the last 30 years. Embracing self-advocacy. Podcast — Ride for acromegaly: 1, miles down; miles to go.
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