Skip to main content

Functional tooth number in the posterior region associated serum ucOC levels



The purpose of this study was to investigate serum undercarboxylated osteocalcin (ucOC) levels in partially edentulous patients scheduled to receive implant treatment and determine the association between ucOC levels, vegetable intake, vitamin K, dietary fiber intake, and functional tooth number in the posterior region (p-FTN).


A total of 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) were included. The association among serum ucOC levels, vegetable intake, vitamin K and dietary fiber intake was assessed using Spearman’s rank correlation coefficient and binary logistic regression analysis.


In total, 35% of patients (16/46 subjects) showed an abnormally high ucOC level ( 4.5 ng/mL). p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively) and a significant negative correlation with ucOC levels (r = − 0.51). Multivariate analysis demonstrated that p-FTN as well as vitamin K intake showed a significant negative association with serum ucOC levels.


More than one-third of patients showed abnormally high ucOC levels. p-FTN showed a negative association with serum ucOC levels, which indicated the possibility that oral status affected bone quality.


Dental implant treatment indicates a high survival rate, and significantly improves oral health-related quality-of-life [1]. Direct structural and functional connection between the living bone and implant surface is fundamental to implant treatment [2]. To assess bone condition, CT scan-based classification is commonly used [3]. On the other hand, the National Institutes of Health proposed that bone strength primarily reflects the integration of bone density and bone quality. Additionally, architecture, turnover, damage accumulation, and mineralization were listed as factors that determine bone quality [4]. However, a previous study reported the application of bone turnover markers (BTMs) for implant treatment [5], but sufficient evidence had not been established and further studies were required.

Osteocalcin (OC) is one of the BTMs produced by osteoblasts and the most abundant non-collagenous protein in bone [6]. OC undergoes g-carboxylation by vitamin K, and glutamic acid (Glu) residues are converted into γ-carboxyglutamic acid (Gla) [7]. Carboxylated osteocalcin binds calcium directly. However, undercarboxylated osteocalcin (ucOC) lacks the ability to bind to the mineral hydroxyapatite, which is released into the circulation [8]. Consequently, serum ucOC levels are negatively correlated with vitamin K intake, and are used clinically as an indicator of vitamin K status [9]. Vitamin K consists of vitamins K1, 2, 3, 4, and 5. Both vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) occur in nature. Green leafy vegetables and seaweeds are rich in vitamin K1, whereas fermented foods are rich in vitamin K2, and bacteria in the gut also synthesize vitamin K2 [10, 11]. Higher ucOC levels are related to lower bone mineral density (BMD) as well as a higher risk of hip fracture [12, 13]. Furthermore, Tanaka et al. found an association between higher ucOC and poor bone strength using quantitative ultrasound in women [14].

The serum ucOC level is affected by several factors. For example, warfarin sodium increases the serum ucOC level through the inhibition of vitamin K functions [15]. In contrast, other medications, such as corticosteroids and bone resorption inhibitors, can decrease the serum ucOC level [16]. Furthermore, it was reported that gastrectomy and Crohn's disease increased serum ucOC levels, which suggested that digestive hypofunction resulted in increased undercarboxylated osteocalcin through vitamin K hypoabsorption and alteration of intestinal flora [17, 18]. Oral function plays a critical role in digestion, and it affects food variety intake and intestinal flora, therefore oral function may also be associated with serum ucOC levels; however, this has yet to be proven.

In this study, we aim to determine insights into ucOC levels in partially edentulous patients scheduled to receive implant treatment, and the association between serum ucOC levels, vitamin K intake and functional tooth number in the posterior region (p-FTN).


Study population

This study included 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) drawn from the Kyushu Dental University Hospital in Japan. The inclusion criteria included partially edentulous patients scheduled to receive implant treatment in the posterior region and had consented to participate in this study. The exclusion criteria included: (1) patients prescribed warfarin sodium or corticosteroids; (2) patients prescribed osteoporosis treatment; (3) patients with gastric or intestinal resection; (4) patients who wore a removable partial denture; (5) patients with anterior tooth loss and without a prosthesis in the anterior region; (6) patients with one or more teeth with “hyper mobility” (class 3 mobility according to Miller’s classification) [19]; and (7) participants who had not given consent.


p-FTN included functional natural tooth, pontic and dental implant crown in the posterior region, and excluded remaining root and wisdom tooth. Vegetable intake, vitamin K, and dietary fiber intake were assessed using a brief self-administered diet history questionnaire (BDHQ). The BDHQ is a questionnaire that consisted of 75 questions (55 questions that related to food consumption and 17 to cooking and dietary behaviors); it assessed dietary habits over the past month [20]. Nutrient intake was calculated from the results of the BDHQ questionnaire using an ad hoc computer algorithm [21]. In order to compensate for declaration error, results were energy-adjusted using estimated energy requirement; energy-adjusted intake = intake /energy intake × estimated energy requirement. Serum ucOC levels were measured by electrochemiluminescence immunoassay.

Statistical analyses

Spearman’s rank correlation coefficient and binary logistic regression analysis were performed. In binary logistic regression analysis, the binary outcomes of abnormally high ucOC ( 4.5 ng/mL) = 1 and normal ucOC (< 4.5 ng/mL) = 0 were employed as the dependent variable. Statistical analyses were computed using BellCurve for Excel (Social Survey Research Information Co., Ltd., Tokyo, Japan); α = 0.05 was considered significant.


Subject characteristics and outcomes

The characteristics of subjects and outcomes are shown in Table 1. The median p-FTN, vegetable intake, vitamin K, dietary fiber intake, and serum ucOC levels were 13, 255.1 g/day, 356.0 μg/day, 13.9 g/day, and 3.94 ng/mL, respectively (Table 1). The percentage of subjects who did not reach the recommended volume was 82.3% (38/46 subjects), 26.1% (12/46 subjects), and 91.3% (42/46 subjects) for vegetable intake (recommended volume in Japan: 350 g/day), vitamin K (recommended volume for osteoporosis prevention in Japan: 250 μg/day) and dietary fiber (recommended volume in Japan: male 21 g/day, female: 18 g/day), respectively. The ucOC levels in 35% of subjects (16/46 subjects) showed an abnormally high value ( 4.5 ng/mL) [22]).

Table 1 Characteristics of subjects and outcomes

Correlation between outcomes

The correlation diagram between p-FTN, vegetable intake, vitamin K intake, dietary fiber intake, and ucOC levels, and results from the Spearman’s rank correlation coefficient are shown in Fig. 1 and Table 2. p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively). p-FTN, vegetable intake, vitamin K and dietary fiber intake showed a significant negative correlation with ucOC levels (r = − 0.51, − 0.35, and − 0.34, respectively). Vitamin K and dietary fiber intake were strongly associated with vegetable intake (r = 0.69 and 0.75, respectively).

Fig. 1
figure 1

Correlation between outcomes. A Correlation between p-FTN and vegetable intake (r = 0.28, p = 0.064). B Correlation between p-FTN and vitamin K (r = 0.21, p = 0.17). C Correlation between p-FTN and dietary fiber intake (r = 0.14, p = 0.36). D Correlation between p-FTN and ucOC level (r = − 0.51, p < 0.001). E Correlation between vitamin K intake and ucOC level (r = − 0.60, p < 0.001)

Table 2 Correlations between outcomes (Spearman’s rank correlation coefficient)

Multivariate analysis of serum ucOC

Binary logistic regression analysis was used to identify the relationship between ucOC levels and other outcomes and age and sex as confounders. The results indicated that both p-FTN [odds ratio = 0.60, 95% confidence interval (CI) = 0.38–0.95] and vitamin K intake (odds ratio = 0.18, 95%CI = 0.035–0.95) showed significant negative association with ucOC levels (Table 3).

Table 3 Binary logistic regression analysis with serum ucOC level as the dependent variable


The use of BTMs indicated bone formation and resorption, which has an important role in the management of osteoporosis [23]. During implant treatment, systematic diseases that impair bone turnover, such as diabetes, exacerbate the peri-implant tissue conditions [24]. A recent study that investigated BTMs in subjects who were scheduled to receive implant treatment demonstrated that almost 50% of subjects showed abnormal BTMs, and bone-specific alkaline phosphatase (BAP) and cross-linked N-telopeptide of type I collagen (NTX) were frequently abnormally high [5]. Our results show that more than one-third of partial edentulous subjects show abnormally high ucOC, which suggests that clinicians must improve awareness of ucOC levels in advance of implant treatment. It was reported that nutritional therapy with vitamin K1 effectively decreases ucOC [25]. Vitamin K2 intake from fermented food represented by Natto could also decrease ucOC [26]. Furthermore, vitamin K2 enabled bone microstructural and mechanical properties in the ovariectomized model rat [27]. Considering the above, preimplant-surgery dietary counseling should be considered.

Although a lot of studies have investigated the association between ucOC, vitamin K, bone quality, and related factors, this study is the first report to suggest the possibility that oral status affects serum ucOC levels. Tooth loss affects food intake and decreases vegetable intake [28, 29]. Vegetable intake, especially green leafy vegetables, are rich in vitamin K1, decreased p-FTN might induce high ucOC in this study. Decreased vegetable intake results in both reduced vitamin K intake and dietary fiber intake [28,29,30]. It is known that dietary fiber consumed by gut bacteria affects the composition and diversity of gut microbiota as well as microbial metabolic activities, including the production of fermentative end products [31]. Although the direct association between dietary fiber consumption and vitamin K production has not been previously described, the present results suggest that increased dietary fiber intake potentially decreases ucOC through enhanced vitamin K production in the gut. Future studies that include microbiota analysis are required.

It was reported that gastrectomized patients showed lower BMD and higher fracture risk than those without [32]. Vitamin D deficiency and secondary hyperparathyroidism have been proposed as common mechanisms for BMD impairment in gastrectomized patients [33]. Alternately, some studies proposed an association between ucOC and vitamin K dissolution and absorption: Ivaska et al. and Iki et al. found abnormal high ucOC in patients with a history of gastrectomy, and it was speculated that an elided or a shortened passage through the duodenum resulted in reduced absorption of vitamin K [12, 34]. The dissolution into dietary lipid is required to absorb lipid-soluble vitamins, including vitamin K [35], and oral function, including crushing and mixing food, plays an important role in lipid-soluble vitamin dissolution. Therefore, decreased p-FTN could induce high ucOC via impaired vitamin K dissolution and absorption. Several previous studies had demonstrated a negative association between tooth number and osteoporosis status [36,37,38]; however, the underlying mechanism was unknown. Results of the present study demonstrate the possibility that tooth loss may induce the progression of osteoporosis due to the increase in ucOC levels.

There are several limitations to this study. The absence of serum vitamin K level is a limitation of this study. Serum ucOC measurement is a well-established method used in clinical examination and research as a biochemical marker of vitamin K insufficiency. Hence, we measured the serum ucOC level in this study. In contrast, serum vitamin K fraction analysis can evaluate vitamin K1 and K2, including the subtypes. Further study should include vitamin K fraction analysis to provide more details on how p-FTN associates with vitamin K. Our results demonstrated an association between p-FTN and vitamin K insufficiency. However, as this was a cross-sectional study, a causal relationship cannot be proven. Furthermore, it remains unknown if prosthodontic interventions contribute to a decrease in the serum ucOC level. Future longitudinal and intervention studies are warranted.


In this study, we demonstrate that p-FTN, as well as vitamin K levels, exhibit a negative association with serum ucOC levels. It is probable that oral status impacts bone quality through ucOC levels.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.


  1. Kurosaki Y, Kimura-Ono A, Mino T, Arakawa H, Koyama E, Nakagawa S, Nguyen HTT, Osaka S, Saeki M, Minakuchi H, Ono M, Maekawa K, Kuboki T. Six-year follow-up assessment of prosthesis survival and oral health-related quality of life in individuals with partial edentulism treated with three types of prosthodontic rehabilitation. J Prosthodont Res. 2021;65:332–9.

    Article  Google Scholar 

  2. Brånemark PI. Osseointegration and its experimental background. J Prosthet Dent. 1983;50:399–410.

    Article  Google Scholar 

  3. Misch C. Contemporary implant dentistry. 2nd ed. St Louis: Mosby; 1999.

    Google Scholar 

  4. NIH consensus development panel on osteoporosis prevention, diagnosis, and therapy. osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785–95.

  5. Yasuda K, Okada S, Okazaki Y, Hiasa K, Tsuga K, Abe Y. Bone turnover markers to assess jawbone quality prior to dental implant treatment: a case-control study. Int J Implant Dent. 2020;6:67.

    Article  Google Scholar 

  6. Hauschka PV, Reid ML. Timed appearance of a calcium-binding protein containing gamma-carboxyglutamic acid in developing chick bone. Dev Biol. 1978;65:426–34.

    Article  Google Scholar 

  7. Cairns JR, Price PA. Direct demonstration that the vitamin K-dependent bone Gla protein is incompletely gamma-carboxylated in humans. J Bone Miner Res. 1994;9:1989–97.

    Article  Google Scholar 

  8. Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin-dependent proteins in bone. Physiol Rev. 1989;69:990–1047.

    Article  Google Scholar 

  9. Yamauchi M, Yamaguchi T, Nawata K, Takaoka S, Sugimoto T. Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women. Clin Nutr. 2010;29:761–5.

    Article  Google Scholar 

  10. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients. 2020;12:1909.

    Article  Google Scholar 

  11. Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6:1971–80.

    Article  Google Scholar 

  12. Szulc P, Arlot M, Chapuy MC, Duboeuf F, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res. 1994;9:1591–5.

    Article  Google Scholar 

  13. Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone. 1996;18:487–8.

    Article  Google Scholar 

  14. Tanaka N, Arima K, Nishimura T, Tomita Y, Mizukami S, Okabe T, Abe Y, Kawashiri SY, Uchiyama M, Honda Y, Tsujimoto R, Kanagae M, Osaki M, Aoyagi K. Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women. J Physiol Anthropol. 2020;39:9.

    Article  Google Scholar 

  15. Bach AU, Anderson SA, Foley AL, Williams EC, Suttie JW. Assessment of vitamin K status in human subjects administered “minidose” warfarin. Am J Clin Nutr. 1996;64:894–902.

    Article  Google Scholar 

  16. Mokuda S, Okuda Y, Onishi M, Sawada N, Matoba K, Yamada A, Jouyama K, Takasugi K. Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels. J Endocrinol Invest. 2012;35:661–4.

    PubMed  Google Scholar 

  17. Miller SC. Textbook of Periodontia. Philadelphia: Blakiston Co; 1950. p. 91.

    Google Scholar 

  18. Iki M, Fujita Y, Kouda K, Yura A, Tachiki T, Tamaki J, Sato Y, Moon JS, Hamada M, Kajita E, Okamoto N, Kurumatani N. Increased risk of osteoporotic fracture in community-dwelling elderly men 20 or more years after gastrectomy: the Fujiwara-kyo osteoporosis risk in Men (FORMEN) cohort study. Bone. 2019;127:250–9.

    Article  Google Scholar 

  19. Sugimoto K, Ikeya K, Iida T, Kawasaki S, Arai O, Umehara K, Watanabe F, Tani S, Oishi S, Osawa S, Yamamoto T, Hanai H. An increased serum N-terminal telopeptide of type I collagen, a biochemical marker of increased bone resorption, is associated with infliximab therapy in patients with Crohn’s disease. Dig Dis Sci. 2016;61:99–106.

    Article  Google Scholar 

  20. Sasaki S, Yanagibori R, Amano K. Validity of a self-administered diet history questionnaire for assessment of sodium and potassium: comparison with single 24-hour urinary excretion. Jpn Circ J. 1998;62:431–5.

    Article  Google Scholar 

  21. Ogawa K, Tsubono Y, Nishino Y, Watanabe Y, Ohkubo T, Watanabe T, Nakatsuka H, Takahashi N, Kawamura M, Tsuji I, Hisamichi S. Validation of a food-frequency questionnaire for cohort studies in rural Japan. Public Health Nutr. 2003;6:147–57.

    Article  Google Scholar 

  22. Shiraki M, Aoki C, Yamazaki N, Ito Y, Tsugawa N, Suhara Y, Okano T. Clinical assessment of undercarboxylated osteocalcin measurement in serum using an electrochemiluminescence immunoassay: establishments of cut-off values to determine vitamin K insufficiency in bone and to predict fracture leading to clinical use of vitamin K2. Iyaku Yakugaku. 2007;57:537–46.

    Google Scholar 

  23. Nishizawa Y, Ohta H, Miura M, Inaba M, Ichimura S, Shiraki M, Takada J, Chaki O, Hagino H, Fujiwara S, Fukunaga M, Miki T, Yoshimura N. Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis. J Bone Miner Metab. 2013;31:1–15.

    Article  Google Scholar 

  24. Yamazaki S, Masaki C, Nodai T, Tsuka S, Tamura A, Mukaibo T, Kondo Y, Ono K, Hosokawa R. The effects of hyperglycaemia on peri-implant tissues after osseointegration. J Prosthodont Res. 2020;64:217–23.

    Article  Google Scholar 

  25. Kuwabara A, Nagae A, Kitagawa M, Tozawa K, Kumode M, Tanaka K. Nutritional therapy with vitamin K1 is effective in the improvement of vitamin K status and bone turnover markers in patients with severe motor and intellectual disabilities. J Nutr Sci Vitaminol (Tokyo). 2020;66:278–84.

    Article  Google Scholar 

  26. Fujita Y, Iki M, Tamaki J, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Tomioka K, Okamoto N, Kurumatani N. Association between vitamin K intake from fermented soybeans, natto, and bone mineral density in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study. Osteoporos Int. 2012;23:705–14.

    Article  Google Scholar 

  27. Iwamoto D, Masaki C, Shibata Y, Watanabe C, Nodai T, Munemasa T, Mukaibo T, Kondo Y, Hosokawa R. Microstructural and mechanical recovery of bone in ovariectomized rats: the effects of menaquinone-7. J Mech Behav Biomed Mater. 2021;120: 104571.

    Article  Google Scholar 

  28. Wakai K, Naito M, Naito T, Kojima M, Nakagaki H, Umemura O, Yokota M, Hanada N, Kawamura T. Tooth loss and intakes of nutrients and foods: a nationwide survey of Japanese dentists. Community Dent Oral Epidemiol. 2010;38:43–9.

    Article  Google Scholar 

  29. Yoshida M, Kikutani T, Yoshikawa M, Tsuga K, Kimura M, Akagawa Y. Correlation between dental and nutritional status in community-dwelling elderly Japanese. Geriatr Gerontol Int. 2011;11:315–9.

    Article  Google Scholar 

  30. Krall E, Hayes C, Garcia R. How dentition status and masticatory function affect nutrient intake. J Am Dent Assoc. 1998;129:1261–9.

    Article  Google Scholar 

  31. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8:172–84.

    Article  Google Scholar 

  32. Yoo SH, Lee JA, Kang SY, Kim YS, Sunwoo S, Kim BS, Yook JH. Risk of osteoporosis after gastrectomy in long-term gastric cancer survivors. Gastric Cancer. 2018;21:720–7.

    Article  Google Scholar 

  33. Oh HJ, Yoon BH, Ha YC, Suh DC, Lee SM, Koo KH, Lee YK. The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis. Osteoporos Int. 2020;31:267–75.

    Article  Google Scholar 

  34. Ivaska KK, Huovinen V, Soinio M, Hannukainen JC, Saunavaara V, Salminen P, Helmiö M, Parkkola R, Nuutila P, Kiviranta R. Changes in bone metabolism after bariatric surgery by gastric bypass or sleeve gastrectomy. Bone. 2017;95:47–54.

    Article  Google Scholar 

  35. Kim JE, Ferruzzi MG, Campbell WW. Egg consumption increases vitamin E absorption from co-consumed raw mixed vegetables in healthy young men. J Nutr. 2016;146:2199–205.

    Article  Google Scholar 

  36. Laudisio A, Marzetti E, Antonica L, Settanni S, Georgakakis I, Bernabei R, Franceschi C, Zuccalà G. Masticatory dysfunction is associated with osteoporosis in older men. J Clin Periodontol. 2007;34:964–8.

    Article  Google Scholar 

  37. Darcey J, Horner K, Walsh T, Southern H, Marjanovic EJ, Devlin H. Tooth loss and osteoporosis: to assess the association between osteoporosis status and tooth number. Br Dent J. 2013;214:E10.

    Article  Google Scholar 

  38. Hasegawa Y, Tsuji S, Nagai K, Sakuramoto-Sadakane A, Tamaoka J, Oshitani M, Ono T, Sawada T, Shinmura K, Kishimoto H. The relationship between bone density and the oral function in older adults: a cross-sectional observational study. BMC Geriatr. 2021;21:591.

    Article  Google Scholar 

Download references


This work was supported by a Grant from the Japan society for the promotion of science KAKENHI (No. 21K10024).

Author information

Authors and Affiliations



MN, YK, TN, FN-A, TN, TM, TM CM and RH conceived the ideas; MN YK and FN-A collected the data; MN, YK and FN-A analyzed the data; MN, YK and CM led the writing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yusuke Kondo.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Kyushu Dental University (approval number: 21-47). All participants provided informed consent to participate in the study.

Competing interests

The authors declare no conflict of interest associated with this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakamura, M., Kondo, Y., Nakamoto, T. et al. Functional tooth number in the posterior region associated serum ucOC levels. Int J Implant Dent 8, 50 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: