Amaç: Akromegali hastalarında kemik mineral densitometre (kmd) ve periodontit varlığını ve etkileşimde bulunan faktörleri değerlendirmek. Gereç ve Yöntem

Yüklə 106.25 Kb.
Pdf просмотр
ölçüsü106.25 Kb.

Turkish Journal of Endocrinology and Metabolism, published by Galenos Publishing.

Original Article


Amaç: Akromegali hastalarında kemik mineral densitometre (KMD) ve periodontit varlığını ve etkileşimde bulunan faktörleri değerlendirmek. 

Gereç ve Yöntem: Kalsiyum-kemik metabolizmasını etkileyen durumu olmayan 47 akromegali olgusu ve 60 yaş-cinsiyet eşleşmiş sağlıklı olgu 

çalışmaya alındı. Yaş, cinsiyet, akromegali süresi ve aktivitesi, geçmiş ve güncel tedaviler, hipofiz hormon profilleri ve replasman tedavileri, 

periodontal analiz sonuçları kaydedildi.

Bulgular: Yaş ortalamaları 46,6±11,5 yıl olan 18 erkek (%38,3), 29 kadın (%61,7) olgunun 25’inin (%53,1) aktif, 22’sinin (%46,8) inaktif hastalığı vardı. 

İnaktif hastalık grubu daha yaşlı idi, hastalık süreleri daha uzundu, sırası ile; p=0,04, p=0,003. Serum kalsiyum, fosfor düzeyleri, 24 saatlik idrar 

kalsiyum atımları, femoral ve lomber KMD değerleri ile hastalık aktivitesi ilişkisizdi (p>0,05). Altı hastada (%12,76) osteoporoz saptandı. Periodontit 

kontrol grubunda daha sık izlendi; %66,7 ve % 44,7, bu grupta ağırlıklı olarak şiddetli periodontit görüldü; %43,3 ve %12.8, (sırası ile; p=0,022, 

p=0,0001). Kronik periodontit sıklığı ve şiddeti, aktif ve inaktif akromegali grupları arasında farksızdı; %48 ve %40,9 (p=0,279). Tekrarlayan 

değerlerin varyans analizi testinde, zaman içinde büyüme hormonu değişimi ve periodontit alt grupları anlamlı dağılım göstermedi (p>0,05).  


Address for Correspondence: Hülya Serinsöz MD, Başkent University Faculty of Medicine, Department of Endocrinology, Adana, Turkey


Received: 25/07/2014 Accepted: 02/02/2015

Purpose: To evaluate bone mineral density (BMD) measurements and the presence of periodontitis in patients with acromegaly, as well as to 

inquire the impact of interfering factors. 

Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 

age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone 

profiles, replacement therapies, and the results of periodontal analysis were recorded. 

Results: Eighteen patients were male (38.3%), 29 were female (61.7%). The mean age of the patients was 46.6±11.5 years, twenty-five (53.1%) 

had active, 22 (46.8%) had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively). Serum 

calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with 

disease activity (p>0.05). Osteoporosis was detected in 6 patients (12.76%). Periodontitis and advanced periodontitis were more common in 

control group (66.7% vs. 44.7%), (43.3% vs. 12.8%) (p=0.022, p=0.0001, respectively). There was no difference in chronic periodontitis and severity 

between active and inactive groups (48% vs. 40.9%; p=0.279). No difference was noted in other study parameters, as well. Repeated measures 

analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups.  

Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. 

Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the 

presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have 

a protective role against periodontitis. 

Turk Jem 2015; 19: 42-48

Key words: Acromegaly, bone, growth hormone (GH), periodontitis, osteoporosis

Conflicts of Interest: The authors reported no conflict of interest related to this article.

Abs tract

Başkent University Faculty of Medicine, Department of Endocrinology, Adana, Turkey

*Başkent University Faculty of Dentistry, Department of Periodontology, Adana, Turkey

**Başkent University Faculty of Medicine, Department of Endocrinology, Ankara, Turkey

Hülya Serinsöz, Melek Eda Ertörer, Sibel Başcıl*, Okan Bakıner, Emre Bozkırlı, Neslihan B. Tütüncü**

Akromegali ve Düşük Periodontit Sıklığı: Büyüme Hormonunun Koruyucu 

Etkisi Olabilir

Low Prevalence of Periodontitis in Acromegaly: Growth Hormone 

May Exert a Protective Effect 

DOI: 10.4274/tjem.2687


Turk Jem 2015; 19: 42-48


Acromegaly is a disorder characterized by growth of many tissues 

due to uncontrolled oversecretion of growth hormone (GH) and 

insulin-like growth factor-1 (IGF-1) (1). Both GH and IGF-1 play 

important roles in calcium and bone metabolism at many steps. 

For instance, IGF-1 activates renal 1-hydroxylase enzyme and 

inhibits 24-hydroxylase, thus, increases serum calcitriol. 

Acromegaly causes periosteal new bone formation, cortical 

thickening of the diaphysis of the long bones and joint space 

widening. Bone mineral density (BMD) is usually unpredictable 

due to interfering factors, predominantly accompanying 

hypogonadism in acromegaly (2,3). Eugonadal acromegalic 

patients exhibit increased cortical bone BMD at the distal radius

whereas spinal trabecular bone usually demonstrate insignificant 

change (4). In eugonadal acromegalic patients, serum osteocalcin, 

urinary hydroxyproline and pyridinoline levels are detected to be 

high and lumbar BMD values are within normal limits (5). 

In acromegaly, osteoporosis is usually due to accompanying 

hypogonadism and results in decrease in lumbar vertebral 

BMD. Disease duration, serum IGF-1 levels and hypogonadism 

predict the prevalence of vertebral fractures (VF) (1,3). However, 

a high rate of  incident VF has been reported in both active and 

controlled acromegalic patients. In a recent study, progression 

of VF has been documented in 20% of cases, despite long-term 

biochemical control of acromegaly. Progression of VF has not 

been detected to relate with BMD values or BMD changes over 

time (6). 

Besides frontal bossing and changes in the lips and nose, 

growth of the mandibular bone, separation of the teeth, maxillary 

widening, and malocclusion of the mouth are frequently 

observed in acromegaly (1). Tooth mobility and loss, interdental 

spaces (diestema), and, rarely, gingival overgrowth are detected 

at periodontal examination. There is scant data about the 

periodontal findings in cases with acromegaly. 

Periodontal disease is a localised inflammatory reaction of the 

tissues surrounding the teeth against bacterial infections (7). 

Its presence may be a risk factor for ischemic heart disease, 

pulmonary diseases, premature labor, and low birth weight. 

Other risk factors associated with periodontal disease are 

smoking, traumatic occlusion of the mouth and diabetes mellitus 

(8). It is the second well-identified cause for tooth loss and usually 

accompanies systemic diseases and is mainly separated into two 

main groups; gingivitis and periodontitis. 

Gingivitis is an immune response against the microbial dental 

plaque located on the teeth and affects more than 90% of the 

population. Smoking, medications, pregnancy and hormonal 

changes during puberty may act on gingiva. Destruction is limited 

to gingiva and is reversible. Gingiva is found to be edematous 

and hyperemic (7,9). However, periodontitis is characterised by 

irreversible injury in periodontal tissues. Diestema and prominent 

tooth mobility are clear signs of periodontitis. Increment in 

probing depth, loss of attachment and demonstration of bone 

loss radiographically are required for the diagnosis. Periodontitis 

is a multifactorial disease and presence of periodontopathogenic 

bacteria is not the only factor necessary for its initiation and 

progression (10). Systemic diseases; cardiovascular diseases, 

diabetes mellitus, syndromes associated with neutropenia, 

rheumatoid arthritis, medications, and accompanying genetic 

and environmental factors may impact the pathogenesis of 

periodontitis and the response of the host to therapy (11). 

Studies inquiring the association between periodontitis and 

systemic bone density reveal that subjects with low bone density 

have less number of teeth, more clinical attachment loss and 

more periodontitis. Low systemic bone density has been proposed 

to be a risk factor for progression of alveolar bone loss and has 

been claimed to increase vulnerability to periodontal destruction. 

An association has also been shown between serum estrogen 

levels and alteration in alveolar bone mineral density among 

post-menopausal women (12,13,14). 

High serum GH, IGF-1, insulin-like growth hormone-binding 

protein-3 (IGF-1BP-3) and calcitriol levels directly act on bone and 

connective tissue in acromegaly. Accompanying hypogonadism, 

defects in glucose metabolism, malabsorption due to somatostatin 

analogues, which are used in acromegaly treatment, may all 

adversely affect the periodontal structures and bone. Besides 

hormonal changes, duration and activity of the disease may affect 

the course of periodontitis (5,15,16). 

In this study, we aimed to evaluate BMD and the presence of 

periodontitis in patients with acromegaly and to inquire the impact 

of interfering factors. 

Materials and Methods 

This study was performed at outpatient endocrinology clinics of 

Başkent University Faculty of Medicine, Adana, Turkey between 

August 2010 and November 2012. 

A total of 47 patients with the diagnosis of acromegaly and 60 

age-matched healthy controls were included for periodontal 

analysis. The study was approved by the Local Ethics Committee 

(tracking #: K09/330) and all participants gave written informed 


The exclusion criteria included having any condition known 

to affect calcium and bone metabolism, such as being on 

Tartışma: Çalışmamızda aşikar hipogonadizm dışlandığında akromegalinin vertebral KMD üzerine negatif etkisi olmadığı gösterildi. Hastalık 

aktivitesinden bağımsız olarak, akromegali olgularının periodontit sıklığı düşük bulundu ve bu bulgu periodontal dokuya negatif etkisi olduğu 

bilinen, eşlik eden durumlarla da değişmedi. Kronik artmış büyüme hormonu maruziyetinin periodontit bakımından koruyucu olabileceği 

sonucuna varıldı. 

Turk Jem 2015; 19: 42-48

Anah tar  ke li me ler: Akromegali, kemik, büyüme hormone, periodontit, osteoporoz

Çıkar Çatışması: Yazarlar bu makale ile ilgili olarak herhangi bir çıkar çatışması bildirmemiştir.


Serinsöz et al. 

Periodontitis and Acromegaly


Turk Jem 2015; 19: 42-48

levothyroxine suppression therapy due to differentiated thyroid 

carcinoma, chronic renal failure, hyperparathyroidism, untreated 

hypothyroidism and/or hypocortisolism, and bisphosphonate 

use. As smoking is known to negatively affect periodontal health, 

it was regarded as an exclusion criterion, as well. Additionally, the 

participants were instructed not to use any interfering medication, 

such as anti-inflammatory and immune-suppressive drugs 

throughout the study period. 

Physical examination was performed and all the exclusion criteria 

were also applied for the participants in control group. 

An acromegalic male with central hypogonadism who used 

testosterone replacement therapy irregularly and another 

male with cured acromegaly who had celiac disease were not 

included. Two other acromegalic males with active disease were 

also excluded because of their total prosthesis. 

The patients were evaluated regarding age, gender, duration and 

activity of acromegaly, past therapy options; medical, surgical, 

radiotherapy, combination therapies, current medical agents, 

pituitary hormone profiles, and replacement therapies. 

Active acromegaly was defined if randomly measured GH was 

above 2.5ng/dl and IGF-1 above age-corrected limits with/without 

medical treatment. Patients with discordant measurements were 

considered as active, as well. Other pituitary functions were 

determined by evaluating pituitary hormones with end organ 

responses and performing dynamic tests where required (17). 

Accompanying glucose metabolism disorders; impaired fasting 

glucose, impaired glucose tolerance as well as diabetes mellitus, 

hypertension and cardiovascular disease were also recorded. 

In study group, patients who were on levothyroxine treatment 

due to central hypothyroidism with normal free thyroxine levels 

were considered euthyroid. Premenopausal women with central 

hypogonadism who were on cyclic estrogen/progesterone 

therapy were regarded as eugonadal as well as the men who 

were on testosterone replacement therapy with normal serum 

testosteron levels. 

Serum calcium, phoshporus and 24-hour urinary calcium 

excretion levels were measured. BMD measurement was 

performed at the femoral neck and lumbar spine. 

Study and control groups were both subjected to periodontal 

examination. Periodontal examinations were performed by 

the same experienced periodontist. Periodontal pocket depth 

(presence of an abnormal gingival sulcus near the point at which 

the gums contact a tooth) was evaluated using periodontal probe 

at six different points of each tooth. Individuals with probing pocket 

depth (PPD) between 4 mm and 6 mm and clinical attachment 

level of (CAL=amount of space between attached periodontal 

tissues and a fixed point, usually the cementoenamel junction) 

up to 4 mm were diagnosed as having chronic periodontitis with 

slight to moderate loss of periodontal support. Those with PPD 6 

mm and CAL greater than 4 mm were regarded as having chronic 

periodontitis with advanced loss of periodontal support. Bleeding 

on probing, which was considered as an objective inflammatory 

parameter in periodontitis establishment, was measured using 

the gingival bleeding index (GBI). A GBI of ≤0.1 was considered 

low risk for the development of periodontitis. Tooth mobility levels 

were evaluated and classified as degrees; 1, 2, 3. Radiographic 

examination, tooth loss, diastemas (space or gap between two 

teeth) and malocclusion were also assessed (18,19). 

Laboratory Analyses and BMD Measurements 

GH measurements were performed with immunometric assay 

(Immulite Growth Hormone, Diagnostic Products Corp., CA, USA), 

IGF-1 measurements were done with highly sensitive and specific 

immunoradiometric methods (Diagnostic Systems Laboratories, 

DSL -5600 ACTIVE). Serum calcium and 24-hour urinary calcium 

excretion levels were determined using the colorimetric method 

(Roche Modular P-Roche). Serum phosphorus was analysed via 

phosphomolibdate method (Architect C16000-ABBOTT). 

BMD measurements were performed using dual energy x-ray 

absorptiometry (DXA) (Hologic QDR 4500, Hologic IIc., Waltham, 

MA, USA) at the lumbar vertebra (L1-L4) and femur neck. T and Z 

scores were evaluated using the new NHANES III reference criteria. 

Osteopenia (a T score between -1 and -2.5) and osteoporosis (a 

T score of  less than 2.5) were defined according to the criteria of 

the World Health Organization. 

Statistical Analysis 

The SPSS software (Statistical Package for the Social Sciences, 

version 17.0, SSPS Inc, Chicago, IL, USA) was used for statistical 

analyses. Categorical variables were given as number and 

percentage, continuous variables are presented as means ± 

SD, if distributed normally and as median - minimum-maximum, 

if distributed not normally. Standard descriptive analysis, 

independent samples T-test, the  Wilcoxon test, Chi-square, 

Mann-Whitney U test, Spearman’s correlation coefficient, and the 

repeated measures ANOVA were used where appropriate. A p 

value of less than 0.05 was considered statistically significant. 


A total of 47 acromegalic patients [18 males (38.3%) and 29 

females (61.7%)] with a mean age of 46.6±11.5 years were 

included in study. Fourteen subjects (29.8%) were on medical 

therapy only, whereas 33 (70.2%) were subjected to combination 

therapy, i.e medical therapy following surgery (24-72.2%), medical 

therapy following radiotherapy (1-2.1%), and medical therapy 

following surgery and radiotherapy (8-24.2%). Of the cases on 

medical therapy only; 23 patients (48.9%) were using octreotide, 

21 (44.7%) were on octreotide and cabergoline; dopamine agonist 

simultaneously, and 3 (6.4%) patients were using pegvisomant 


Hormonal assessment of disease activity revealed that 25 

(53.1%) patients had active acromegaly, whereas 22 (46.8%) 

had inactive disease. Inactive acromegaly group was older and 

had longer disease duration (p=0.04 and p=0.003, respectively). 

Serum calcium and phosphorus levels, 24-hour urinary calcium 

excretion and BMD values at the lumbar spine and femur neck 

exhibited insignificant difference between the active and inactive 

acromegaly groups. Details are given in Table 1. 

Twenty-one patients (44.7%) had glucose metabolism disorder at 

various severities. Twenty cases (42.6%) had hypertension and two 

(4.3%) had cardiac disease. Active and inactive disease groups 

did not differ regarding therapeutic options, glucose metabolism 

Serinsöz et al. 

Periodontitis and Acromegaly


Turk Jem 2015; 19: 42-48

disorders and cardiac disease (p=0.457, p=0.202, p=0.123, 

respectively), however, more patients in active acromegaly group 

had hypertension, as might be expected (p=0.042). 

Among 13 female cases with active disease, nine (69.2%) were 

premenopausal, whereas seven (43.8%) were premenopausal 

among 16 female cases with inactive acromegaly (p=0.264). 

Postmenopausal cases were older (57.1±5.1 years vs. 37.7±5.5 

years) and had longer duration of disease [median: 6 (1-17) years 

versus median: 2 (1-12)], as may be expected (p=0.039 and 0.001, 

respectively). However, they exhibited statistically indifferent 

lumbar and femur BMD measurements regarding to disease 

activity and menopausal status (p=0.964, p=0.94 and p=0.188, 

p=0.469, respectively). 

Osteoporosis was detected in 6 subjects (12.76%) in study group. 

One acromegalic man exhibited low femur bone density, whereas 

five patients-two premenopausal and three postmenopausal 

women-demonstrated osteoporosis at the lumbar spine. 

Periodontal examination findings in acromegaly and control 

groups (n=60) were evaluated. Twenty-six patients with 

acromegaly (55.3%) did not exhibit periodontitis. Of 21 patients 

(44.7%) with acromegaly and periodontitis; 15 (31.9%) had slight to 

moderate periodontitis and 6 (12.8%) had advanced periodontitis. 

Twenty-two acromegalic patients (46.8%) exhibited macroglossi. 

More number of cases had periodontitis in control group, 

advanced periodontitis being dominantly (p=0.022 and p=0.0001, 

respectively). Details are given in Table 2. 

There was no difference in the total number of cases with chronic 

periodontitis between active and inactive acromegaly groups 

(48% vs. 40.9%) (p=0.279). There was no statistically significant 

difference in severity of periodontitis between the groups, as well 

(details are shown in Table 3). The presence of periodontitis also 

exhibited any relationship with menopausal state (p=0.521 ). There 

was not a relationship between the presence of periodontitis and 

menopausal state.

Besides similar periodontal findings, active and inactive 

acromegaly groups exhibited statistically insignificant difference 

with regard to calcium-BMD analyses. 

Study parameters in acromegaly patients (n=47) were compared 

with regard to periodontal disease and its severity; 26 subjects 

were without periodontitis, 15 were  with slight to moderate 

periodontitis  and 6 patients were with advanced periodontitis. 

There was no difference between the groups in terms of serum 

calcium and phosphorus levels, final GH and IGF-1 levels, 

presence of hypertension, glucose metabolism disorder and/or 

cardiac disease (p=0.121, p=0.604, p=0.590, p=0998, p=0.253, 

p=0.081, and p=0.782, respectively). 

Considering the negative impact of glucose metabolism disorders 

on periodontal structures, acromegaly cases were compared with 

Serinsöz et al. 

Periodontitis and Acromegaly

Tablo 3. Distribution of periodontitis in acromegaly group regarding disease activity


Cases without periodontal 

pathology (n)

Cases with slight to moderate chronic 

periodontitis (n)

Cases with advanced 

periodontitis (n)

Active Acromegaly 





Inactive Acromegaly 









Table 1. Comparison of general features and bone parameters of 

active and inactive acromegaly patients 

Disease activity


Active group 


Inactive group 



Age (years)




Gender (F/M) (%)




Duration of acromegaly 


2 (1-10)

5 (2-17)


Serum GH (ng/ml)

4.01 (0.38-56)

0.82 (0.09-2.4)


Serum IGF-1 (ng/ml)

417 (232-1356) 

173 (57-252)


Serum Ca (mg/dl)




Serum P (mg/dl)




Urinary Ca (mg/day)

105 (10-380)

105 (10-300)


Lumbal T score (total)

-0.9 (-4.0-2.0)

-0.65 (-4.0-2.0)


Femoral neck T score

-0.10 (-3.0-2.0)

-0.1 (-2.0-2.0)


GH: Growth hormone, IGF-1: Insulin like growth hormone-1

Mean ± Standard Deviation, Median (Minimum-Maximum)

Table 2. Documentation of general features and periodontological 

examination of Acromegaly group and Control group








Age (year)




Gender (F/M) (n)





Acromegaly (n/n)




Glucose Metabolism  

Disorder n (%)

21/47 (44.7)



Cases without periodontitis  

 n (%)

26/47 (55.3)

20/60 (33.3)


Total # of chronic 

periodontitis n (%) 

21/47 (44.7)

40/60 (66.7)


Slight to moderate 

periodontitis n (%)

15/47 (21.9)

14/60 (23.3)


Advaced periodontitis  n (%)

6/47 (12.8)

26/60 (43.3)


Macroglossi n (%)

22/47 (46.8)




Turk Jem 2015; 19: 42-48

Serinsöz et al. 

Periodontitis and Acromegaly

regard to the presence of glucose metabolism disorder. Keeping 

in accordance with the literature, 13 (61.9%) of 21 patients with the 

disorder was found to have chronic periodontitis, while 8 (38.1%) of 

26 patients with normal glucose metabolism had periodontitis of 

various severity (p=0.043). Presence of other metabolic disorders, 

i.e. hypertension or cardiac disease, was found not to associate 

with periodontitis. 

By taking a T score of 0 as the cut-off value, acromegaly cases 

were grouped as the ones with or without osteoporosis/

osteopenia. Twenty-seven patients (57.4%) had lumbar 

osteoporosis/osteopenia, whereas femoral osteoporosis/

osteopenia was detected in only 15 subjects (31.9%). Disease 

activity exhibited no impact on the presence of osteoporosis/

osteopenia at lumbar and femoral BMD (p=0.533 and p= 0.177, 

respectively). Presence of periodontitis did not show a relationship 

with osteoporosis/osteopenia at either site, as well (p=0.369 and 

p=0.549). Repeated measures analysis of variance performed to 

investigate the relationship between the GH change in time at 

least three sequential time points and periodontitis subgroups 

exhibited (GH change in time at least three sequential time points 

and periodontitis subgroups), statistically insignificant distribution 

[GH (median: minimum-maximum); GH1: 10.0 (0.52-40.0), GH2: 

6.89 (0.38-200), GH3: 4.53 (0.35-56)]. 


GH has been demonstrated to act on bone via interacting directly 

on GH receptors on osteoblasts and via increasing local IGF-1 

production (autocrine and paracrine effect). IG-1 contributes 

to the differentiation of osteoblasts. GH deficiency has been 

demonstrated to associate with bone loss and osteoporosis, 

however, the impact of excess GH on bone tissue is less clear 

(20,21,22). In the present study investigating bone density and 

periodontital tissue, a new site of trabecular bone, among 

acromegaly cases, no statistically difference was found between 

active and inactive acromegaly subgroups in serum calcium 

and phosphorus levels, urinary calcium excretion and BMD 

measurements in the presence of similar rates of periodontitis. 

Periodontitis has been detected less frequently with less severity 

in study group. Severity of periodontitis has also been shown 

not to associate with accompanying metabolic problems, e.g., 

hypertension, cardiac disease or glucose metabolism disorder, 

and with biochemical and hormonal parameters, such as serum 

calcium, phosphorus, GH and IGF-1 levels and menopausal 

status. Thus, acromegaly seems to exert a protective effect against 

periodontitis with neutral effect on vertebral BMD in the absence 

of overt hypogonadism. 

Active acromegaly in the presence of  high serum GH and IGF-1 

levels have been shown to impair bone quality and increase 

the risk of bone fragility. It has been detected to associate with 

hypercalciuria and negative calcium balance (23). High bone 

turnover has been detected by measuring changes in biochemical 

markers of bone metabolism and histomorphometry among 

acromegalic patients. 

Markers for bone turnover, predominantly the resorption 

markers, have been shown to increase and the latter have been 

demonstrated to correlate positively with serum GH and IGF-1 (24). 

However, keeping in accordance with our findings, the negative 

effects mentioned above have not been shown in DXA-BMD 

measurements and normal or even high bone density has also 

been demonstrated in acromegaly (25). 

We have performed a liberal selection bias for excluding 

hypogonadism and found out that disease activity exhibited 

no clear impact on BMD in acromegaly. In addition, there was 

no statistically significant difference between pre-menopausal 

acromegalic patients and their older postmenopausal peers 

in BMD values. Our finding is compatible with the literature 

reporting the neutral effect of acromegaly on vertebral BMD in 

the absence of hypogonadism (4,5). However, one can argue 

that inactive acromegaly cases and the postmenopausal ones 

in this study were older and naturally had longer duration of 

disease, thus, this may have blunted their axial BMDs. DXA, the 

method we performed is currently the most commonly used one 

for determining bone health. However, it has some limitations. 

Atherosclerotic plaques, vertebral deformities and osteoarthritis 

may cause falsely high BMD measurements. Besides, DXA 

measures areal BMD-grams per square centimeter - and 

its 2-dimensional (2D) BMD measurement may probably be 

negatively affected by bone enlargement in acromegaly. It also 

does not give details about cortical and trabecular bone and 

bone micro-architecture which are very important for fracture 

risk assessment (24). High-resolution quantitative computed 

tomography (HR-QCT) is a method that permits the in vivo 

assessment of the bone micro-architecture and the volumetric 

BMD. Its measurements are comparable to 2D histomorphometry 

and 3D microcomputed tomography of transiliac bone biopsies 

(25). In a very recent study, the negative effect of acromegaly has 

been demonstrated on trabecular bone microarchitecture using 

HR-QCT in the distal radius and tibia in eugonadal patients. In 

that study, hypogonadism has been strictly defined and, besides, 

young acromegalics without sex hormone replacement therapy 

and postmenopausal women have also been excluded. This 

approach has resulted in a younger group of patients with shorter 

duration of disease and less contributing factors. However, the 

resultant relatively low number of participants necessitates this 

study to be re-performed on a larger number of eugonadal 

acromegalic patiens by using vertebral HR-QCT (26). 

We were unable to exclude our postmenopausal patients due 

to low number of participants and that may be considered as 

a limitation of our study. However, a complementary parameter, 

periodontal analysis, was performed in addition to DXA to 

investigate an additional area of trabecular-alveolar bone. 

We assume that lower rates of chronic periodontitis among 

acromegalic patients support the reliability of our DXA-BMD 


Our findings impose the idea that in the absence of overt 

hypogonadism, excess GH may not have a negative effect on 

trabecular BMD. Nevertheless, it should be kept in mind that 

normal BMD does not imply a risk-free profile for vertebral 


Turk Jem 2015; 19: 42-48

Serinsöz et al. 

Periodontitis and Acromegaly

fractures. Progression of VF in controlled acromegaly cases with 

normal BMD is a supportive observation for this proposal (6). 

Periodontitis is an important area of interest for periodontists 

due to the fact that it causes irreversible destructive injury to 

alveolar bone and the net effects of GH and IGF-1 on periodontal 

structures are not clear. Osteoblast are regulator cells of bone 

metabolism, they limit bone matrix synthesis or bone resorption 

under various conditions. Human periodontal ligament cells 

(PDL) act like osteoblasts; they are the master cells regulating 

the resorption and synthesis of connective tissue of periodontal 

structures (27,28). GH is an important factor acting on the gingival 

tissue and alveolar bone. Besides their effects on osteoblasts, GH 

and IGF-1 have been demonstrated to increase the secretion of 

bone morphogenic protein-2 (BMP-2) and bone morphogenic 

protein-4 (BMP-4) from human dental pulp fibroblasts (29). GH 

has been reported to increase alveolar bone formation in an 

experimental study on rat periodontium (30). Accordingly, in a 

recent study, acromegalic patients have been shown to exhibit 

less periodontitis (8). This effect may be partially attributed to the 

not negative impact of acromegaly on trabecular bone (4). The 

findings of our study are compatible with the data mentioned 

above. It is possible that chronic exposure to excess GH may 

even have a protective effect against periodontitis. Knowing that 

postmenopausal state is a risk factor for periodontitis, detection 

of similar number of postmenopausal and premenopausal cases 

with periodontitis in our cohort is a supportive data to the above 

mentioned data (14). After grouping our cases with regard to the 

presence of osteoporosis/osteopenia, it was observed that there 

was no difference in the prevalence of periodontitis between the 

groups. We were unable to demonstrate the protective effect of 

chronic excess GH exposure on the periodontal tissue statistically 

by using the repeated measures analysis of variances, however, 

we assume that if the number of acromegalic participants could 

be increased, the statistical significance would be evident. 

Our study has some limitations. The relatively low number of 

participants is one of them, and therefore we had to perform a 

liberal approach regarding the inclusion of hypogonadal patients.

Not performing HR-QCT and not measuring resorption markers 

are the other limitations. 

In conclusion, in the present study, we have demonstrated that 

acromegaly exerts no clear negative impact on vertebral BMD 

in the absence of overt hypogonadism. Regardless of disease 

activity, acromegaly cases exhibit lower rates of periodontitis 

with less severity which remains unchanged in the presence 

of accompanying metabolic disorders known to have negative 

effects on the periodontal tissue. Chronic exposure to excess 

GH may have a protective role against periodontitis. We believe 

this information requires to be confirmed by studies with larger 

sample sizes. 

Acknowledgement: Many thanks to Çağla Sarıtürk for her 

contribution for statistical analysis. 


1.  Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am. 


2.   Kotzmann H, Bernecker P, Hübsch P, Pietschmann P, Woloszczuk W, 

Svoboda T, Geyer G, Luger A. Bone mineral density and parameters of bone 

metabolism in patients with acromegaly. J Bone Miner Res. 1993;8 :459-


3.   Scillitani A, Chiodini I, Carnevale V, Giannatempo GM, Frusciante V, Villella 

M, Pileri M, Guglielmi G, Di Giorgio A, Modoni S,Fusilli S, Di Cerbo A, Liuzzi A. 

Skeletal involvement in female acromegalic subjects: the effects of growth 

hormone excess in amenorrheal and menstruating patients. J Bone Miner 

Res. 1997;12:1729-1736. 

4.   Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities 

in acromegaly: the effects of excess growth hormone and hypogonadism.  

Ann Intern Med. 1989;111:567-573. 

5.   Ezzat S, Melmed S, Endres D, Eyre DR, Singer FR. Biochemical assessment 

of bone formation and resorption in acromegaly. J Clin Endocrinol Metab. 


6.   Claessen KM, Kroon HM, Pereira AM, Appelman-Dijkstra NM, Verstegen 

MJ, Kloppenburg M, Hamdy NA, Biermasz NR. Progression of vertebral 

fractures despite long-term biochemical control of acromegaly: a 

prospective follow-up study. J Clin Endocrinol Metab. 2013;98:4808-4815. 

7.   Brown LJ, Löe H, Prevalence, extent, severity and progression of periodontal 

disease. Periodontol 2000.1993;2:57-71.

8.   Lima DL, Montenegro RM Jr, Vieira AP,  Albano MF, Rego DM. Absence of  

periodontitis in acromegalic patients. Clin Oral Investig. 2009;13:165-169. 

9.   Kinane DF. Causation and pathogenesis of periodontal disease. Periodontol 


10.   Conaghan PG, Brooks P. Disease modifying antirheumatic drugs, including 

methotrexate, gold, antimalarials and  D-penicillamine. Curr Opin 

Rheumatol. 1995;7:167-173. 

11.   Page RC, Kornman KS. The pathogenesis of human periodontitis: an 

introduction. Periodontol 2000.1997;14:9-11. 

12.  Mohammad AR, Hooper DA, Vermilyea SG, Mariotti A, Preshaw PM. An 

investigation of the relationship between systemic bone density and clinical 

periodontal status in post-menopausal Asian-American woman. Int Dent J. 


13.   Yoshihara A, Seida Y, Hanada Y, Miyazaki H. A longitudinal study of the 

relationship between periodontal disease and bone mineral density in 

community-dwelling older adults. J Clin Periodontol. 2004;31:680-684. 

14.   Passos JS, Vianna MI, Gomes-Filho IS, Cruz SS, Barreto ML, Adan L, Rösing 

CK, Cerqueira EM, Trindade SC,  Coelho JM. Osteoporosis/osteopenia as 

an independent factor associated with periodontitis in postmenopausal 

women: a case-control study. Osteoporos Int. 2013;24:1275-1283. 

15.   Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities 

in acromegaly: the effects of excess growth hormone and hypogonadism. 

Ann Intern Med. 1989;111:567-573. 

16.  Kayath MJ, Vieira JG. Osteopenia occurs in a minority of patients with 

acromegaly and is predominant in the spine. Osteoporos Int. 1997;7:226-


17.   Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, 

Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A; 

Acromegaly Consensus Group. Guidelines for acromegaly management: 

an update. J Clin Endocrinol Metab. 2009;94:1509-1517. 

18.   No authors listed. Parameter on chronic periodontitis with slight to moderate 

loss of periodontal support. American Academy of Periodontology. J 

Periodontol. 2000;71:853-855. 

19.   No authors listed . Parameter on chronic periodontitis with advanced loss of 

periodontal support. American Academy of Periodontology. J Periodontol. 


20.  Giustina A, Mazziotti G, Canalis E. Growth hormone, Insulin-like growth 

factors, and the skeleton. Endocr Rev. 2008;29:535-559. 

21.  Isaksson OG, Ohlsson C, Bengtsson BA, Johannsson G. GH and bone-

experimental and clinical studies. Endocr J. 2000;47:9-16. 

22.  Haase HR, Ivanovski S, Waters MJ, Bartold PM. Growth hormone regulates 

osteogenic marker mRNA expression in human periodontal fibroblasts and 

alveolar bone-derived cells. J Periodontal Res. 2003;38:366-374. 

23. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of 

acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 



Turk Jem 2015; 19: 42-48

Serinsöz et al. 

Periodontitis and Acromegaly

24. Ueland T, Fougner SL, Godang K, Schreiner T, Bollerslev J. Serum GH 

and IGF-I are significant determinants of bone turnover but not bone 

mineral density in active acromegaly: a prospective study of more than 70 

consecutive patients. Eur J Endocrinol. 2006;155:709-715. 

25.  Cohen A, Dempster DW, Müller R, Guo XE, Nickolas TL, Liu XS, Zhang 

XH, Wirth AJ, van Lenthe GH, Kohler T, McMahon DJ,Zhou H, Rubin MR, 

Bilezikian JP, Lappe JM, Recker RR, Shane E. Assessment of trabecular 

and cortical architecture and mechanical competence of bone by high-

resolution peripheral computed tomography: comparison with transiliac 

bone biopsy. Osteoporos Int. 2010;21:263-273. 

26.  Madeira M, Neto LV, de Paula Paranhos Neto F, Barbosa Lima IC, Carvalho 

de Mendonça LM, Gadelha MR, Fleiuss de Farias ML. Acromegaly has 

a negative influence on trabecular bone, but not on cortical bone, as 

assessed by high-resolution peripheral quantitative computed tomography. 

J Clin Endocrinol Metab. 2013;98:1734-1741. 

27.  Ogata Y, Niisato N, Sakurai T, Furuyama S, Sugiya H. Comparison of the 

characteristics of human gingival fibroblasts and periodontal ligament cells. 

J Periodontol. 1995;66:1025-1031. 

28.  Ohgi S, Johnson PW. Glucose modulates growth of gingival fibroblasts and 

periodontal ligament cells: correlation with expression of basic fibroblast 

growth factor. J Periodontal Res. 1996;31:579-588. 

29.  Li H, Bartold PM, Zhang CZ, Clarkson RW, Young WG, Waters MJ. Growth 

hormone and insulin-like growth factor I induce bone morphogenetic 

proteins 2 and 4: a mediator role in bone and tooth formation? 

Endocrinology. 1998;139:3855-3862. 

30.  Li H, Bartold PM, Young WG, Xiao Y, Waters MJ. Growth hormone induced 

bone morphogenetic proteins and bone-related proteins in the developing 

rat periodontium. J Bone Miner Res. 2001;16:1068-1076. 

Поделитесь с Вашими друзьями:

Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur © 2019
rəhbərliyinə müraciət

    Ana səhifə