Plasma Osteocalcin Levels, Status of Oral Disease and Alteration in Mandibular Bone Density in Postmenopausal Women

INTRODUCTION

Menopause is often associated with a series of physical changes. Most of these alterations are directly linked to estrogen loss, including vaginal dryness and bone demineralization. Some authors have also reported slight higher prevalence of cardiovascular pathologies in postmenopausal women (PMW). Among PMW, osteoporosis is a prime concern resulting in considerable morbidity and mortality. It has also been reported that more than half of women over the age of 65 years have a compression fracture. Hence, it is necessary to maintain bone mass for preventing the osteoporosis. Vertebral fractures (due osteoporosis in PMW) can also result in loss of height, kyphosis, and lordosis (postural changes).^1–3

It is probably inappropriate to analyze the incidence and statistical data in relation to menopause, as it is a female’s physiologic alteration. However, it increases the risk for development of different pathological lesions. Occurrence of osteoporosis involving the mandible in these patients increases the risk for development of pathologies involving oral soft and hard tissues. This can result in loosening of teeth, thereby increasing the chances of tooth loss. Loss of teeth in the posterior tooth region can lead to loss of neuromuscular stability of the mandible, decrease in masticatory efficiency, poor aesthetics, etc.^4,5

For appreciating the pathophysiologic pathways for bone metabolic pathologies, different biochemical markers of bone metabolism are considered as significant tools. The assessment of the protein fragments produced by osteoblasts (osteocalcin, enzymes produced during osteogenesis: alkaline phosphatase) are of significant importance for analyzing the osteoblastic activity.^6,7

Osteocalcin, which is an osteoblast-specific gene, encodes for a secreted protein and is commonly used as a serum indicator of osteoblastic activity and bone formation. It performs the function of regulating the bone mineralization process.^2,4,7 Osteocalcin is a noncollagenous protein produced by osteoblasts. The osteocalcin protein consists of three residues of the amino acid γ-carboxyglutamic acid (Gla). Assessment of osteocalcin levels could be used for monitoring therapy with antiresorptive agents. Elevated serum osteocalcin levels are commonly seen in patients with chronic kidney disease (due to reduced renal clearance, elevated bone metabolism, or both) as an effect of aging and gender. Also, there might be some other factors that influence the serum osteocalcin levels like oral contraceptives, hormone replacement therapy, diabetes mellitus, and body mass index (BMI). Variation in levels of calcium uptake is also said to affect serum osteocalcin levels. Osteocalcin expression is elevated in metastatic bone tumors including prostate tumors.^4–8 Hence, the present study aimed to assess plasma osteocalcin levels, status of oral disease, and alteration in mandibular bone density in PMW.

MATERIALS AND METHODS

The present study was conducted with the aim of assessing plasma osteocalcin levels, status of oral disease, and alteration in mandibular bone density in PMW. Ethical approval was obtained from institutional ethical committee. Written consent was also obtained from all the participants after explaining in detail the entire research protocol. A total of 160 patients were enrolled. Among these, 80 patients were premenopausal women while the remaining 80 were PMW.

RESULTS

In the present study, 80 PMW and 80 premenopausal patients were enrolled. Mean age of the PMW and premenopausal patients was 53.12 years and 39.36 years, respectively. Mean fasting blood glucose levels of PMW and premenopausal women was found to be 88.6 mg/dL and 80.4 mg/dL, respectively (Fig. 4). While analyzing the plasma osteocalcin levels, it was observed that mean osteocalcin levels of PMW (453.12 ng/mL) were significantly higher in comparison to the premenopausal patients (249.28 ng/mL) (p value < 0.05) as shown in Table 1. Average number of missing teeth in PMW was 7 while in premenopausal women were 2; on comparing, the results were found to be statistically significant (Table 2). Mean attachment loss was 3.1 mm and 2.2 mm in PMW and premenopausal women, respectively. Mean ABL% was 27.8% and 20.4% in PMW and premenopausal women, respectively. On comparing statistically, it was observed that PMW had significantly higher CSOD and number of peri-apical radiolucencies in comparison to premenopausal women. Plasma osteocalcin levels among PMW with MCI of C2 to C3 (435.1 ng/mL) were significantly higher in comparison to PMW with MCI of C1 (321.8 ng/mL) (Fig. 1) as shown in Table 3. It was also seen that mean ABL%, mean number of missing teeth and mean value of clinical attachment loss was significantly higher in PMW with MCI of C2–C3 (Figs 2 and 3) in comparison to patients with index of C1 (Fig. 1) (p value < 0.05). Also, it was observed that BMD as assessed by MCI were found to be negatively and significantly correlated with oral disease status and osteocalcin levels as shown in Table 4. On comparing the MCI in-between the PMW and premenopausal women, significant difference was obtained as shown in Table 5.

DISCUSSION

“Menopause” word is of Greek origin referring to month and cessation. At times, the term is used for describing climacteric, which denotes happenings associated with “the changes in life.” It has been seen that with advancing age, bone mass decreases in humans. In the third and fourth decade of life, human bones show decline in density along with increasing porosity. This is specifically exaggerated in women after the occurrence of menopause. Hence, significantly higher risk of osteoporosis is associated in such women. Data from past studies have also shown that BMD of mandible is affected by mineral levels of skeleton.^16,17

Until the last decade, the association between energy metabolism and osseous tissue was regarded as unidirectional in which there are multifaceted communications between leptin, adiponectin, and neuropeptides. Literature from the animal studies has demonstrated that osseous cells control glucose and fat metabolism through osteocalcin. Osteocalcin is a protein in nature and is found to be present mainly in bone and dentine tissue. It is known to play a crucial role in regulating calcium homeostasis throughout the bone mineralization process. After its formation, a significant proportion of it is assimilated into the bone’s extracellular matrix. However, in systemic circulation, a small proportion of it is released. Hence, it is regarded as a specific marker for demonstrating osteoblastic activity.^4,5,18–20 Hence, the present study was undertaken for assessing plasma osteocalcin levels, status of oral disease, and alteration in mandibular bone density in PMW.

In the present study, 80 PMW and 80 premenopausal women were enrolled. Mean osteocalcin levels of PMW were significantly higher in comparison to the premenopausal women as shown in Table 1. Also, PMW had significantly higher CSOD and number of peri-apical radiolucencies in comparison to premenopausal women (Table 2). Our results were in concordance with the results obtained by Kalaiselvi et al. and Thanakun et al. who also reported similar findings in their respective studies. In the study conducted by Kalaiselvi et al., the authors analyzed correlation between bone remodeling biomarkers and osteocalcin with BMD in nonosteoporotic PMW and osteoporotic women. They analyzed 30 nonosteoporotic (group I) and 30 osteoporotic women. Afterward, they assessed the serum osteocalcin and BMD. In PMW, they observed a negative association among osteocalcin level and the BMD. Also, significant results were obtained by the authors while comparing the mean serum osteocalcin and BMD values among both the study groups.^21,22 In another study conducted by Thanakun et al., authors compared the osteocalcin levels, oral pathologies, and mandibular BMD alterations among PMW and premenopausal women. After analyzing 92 patients, they observed significantly higher osteocalcin levels in PMW in comparison to premenopausal women. Results of their study were in favor of the present study. They also reported significantly higher incidence of oral lesions in PMW. However, in PMW, they reported significantly lower mandibular BMD.²²

In the present study, mean plasma osteocalcin levels among PMW with MCI of C2 to C3 were significantly higher in comparison to PMW with MCI of C1 (Table 3). Also, mean ABL%, mean number of missing teeth and mean value of clinical attachment loss was significantly higher in PMW with MCI of C2 to C3. In the past literature, reliability of MCI as a diagnostic tool has been proved from time to time for screening PMW with osteoporosis. Occurrence of any form of cortical erosion (C2 or C3) could be considered as a valuable indicator of reduced BMD. This is because in nearly more than three-fourth of the population, it is accompanied with a minimum of osteopenia. In a previous study conducted by Gaur et al., the authors showed that a significant relationship exists between BMD and MCI. They observed specificity and sensitivity of be 88.9% and 100%, respectively.^23,24

In the present study, BMD was found to be negatively and significantly correlated with oral disease status and osteocalcin levels (Table 4). Impact of menopause on BMD and mandibular bone width was evaluated by Munakata et al., who evaluated 30 premenopausal women and 42 PMW. They observed that trabecular BMD of PMW was lower in comparison to premenopausal women. They also reported negative correlation between trabecular region width with BMD and positive correlation between cortical width and BMD. Their results showed that both bone (mandible) quality and quantity is affected by menopause.²⁵

Circulating osteocalcin levels are significantly correlated with abdominal obesity and decreased BMD. Synthesis of osteocalcin takes place during bone formation process. However, there is at least partial coupling of bone resorption with bone formation during bone remodeling process. When bone resorption takes place, there is release of osteocalcin into the blood from the bone matrix. It is also hypothesized that osteocalcin is a better marker of bone turnover in comparison to bone formation. In premenopausal women, it is assumed that bone turnover is more or less constant. However, it is altered in PMW leading to elevation in osteocalcin levels. Hence, the increased osteocalcin levels might be more efficient technique for early detection in subjects with rapid bone turnover rates after the onset of menopause.^{11,15,20–22}

In the present study, significant results were obtained while comparing the MCI in-between the two study groups (Table 5). Previous studies have also demonstrated negative correlation of plasma osteocalcin levels with BMI and BMD. In a study conducted by Sternfeld et al., the authors demonstrated that alterations in the menopausal status was not correlated with obesity but was significantly correlated with increased waist circumference.^26,27 In another study conducted by Irie et al., the authors evaluated the impact of menopause on mandibular bone by assessing the morphological alterations in the mandible of ovariectomized rats. However, they not only observed significantly reduction for both bone mass and width of trabecular bone but at the same time also observed significantly augmented distances between trabeculae in ovariectomized rats in comparison to healthy controls.²⁸

The limitations of the present study were that the study had smaller sample size and was of shorter duration. Also, bone mineral density of only mandible was assessed.

CONCLUSION

Under the light of above obtained results, the authors conclude that there is significantly higher prevalence of oral lesions along with oral dryness in postmenopausal women. Also, thinning of mandibular cortex is significantly higher in postmenopausal women. Higher plasma osteocalcin levels help in predicting osteopenia/osteoporosis at an early stage in such women. Hence, we recommend maintaining of adequate oral hygiene and regular health check at timely intervals.

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