A Novel Concept to Promote the Health of Dental Implants: Host-Modulation Therapy
International Journal of Physical Medicine & Rehabilitation

International Journal of Physical Medicine & Rehabilitation
Open Access

ISSN: 2329-9096

Short Communication - (2021)

A Novel Concept to Promote the Health of Dental Implants: Host-Modulation Therapy

Lorne M. Golub*, Hsi-ming Lee and Stephen G. Walker
*Correspondence: Lorne M. Golub, Department of Oral Biology and Pathology, Stony Brook, NY, USA, Email:

Author info »


Of particular interest to the readers of this journal, “Physical Medicine and Rehabilitation”, recent studies (and experience) in the field of “Oral and Dental Rehabilitation”, indicate that Host-Modulation Therapy (HMT), originally developed as adjunctive treatment for the management of microbial-induced inflammatory periodontal disease (periodontitis) around natural teeth, is also likely applicable to promote the health of soft tissues, and jaw bone (mandible/maxilla) supporting dental implants. As background, Host-Modulation Therapy, or HMT, was proposed soon after the wide-spread recognition that the inflammatory response in periodontitis was initiated by specific anaerobic gram-negative microorganisms in the dental biofilm (dental plaque), including, but not only Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola [1]. Soon thereafter, however, the ability of the inflammatory response (triggered by the host tissues responding to the microbial metabolites and toxins notably lipopolysaccharide/ endotoxin) to destroy the largely collagenous periodontal connective tissues (the gingiva, periodontal ligament, and alveolar bone matrix), was linked to excessive production and activity of proteolytic enzymes notably the matrix metalloproteinases. These mediators particularly include the collagenases, MMP-8 and MMP-13, the gelatinase/type IV collagenase, or MMP-9, as well as other neutral proteinases (which are optimally active at physiologic or neutral pH in tissue fluids), including cathepsin G, and leukocyte elastase. The details of these pathologic, host-mediated mechanisms in periodontal diseases were recently described [2-4].

However, dental implants have become a dominant treatment strategy to manage the loss of teeth in adults which is largely the result of periodontitis, not (as is the case in children) due to dental caries or “tooth decay” [5]. In this regard, it has been estimated that 25%-44% of dental implants, which are increasingly and commonly used to replace natural teeth in patient’s jaws, will be significantly compromised by the all-toocommon inflammatory/collagenolytic diseases, perimucositis and periimplantitis [2,4]. Moreover, it is well-recognized in the field that the impact of these two inflammatory diseases, particularly the latter which involves the oral mucosa and the maxillary and mandibular bone supporting the implants, is more severe for periimplantitis than inflammatory disease around natural teeth (periodontitis), and reversal of this inflammation takes longer in perimplant tissues [2,6-9]. In addition, this common dental disease, periodontitis, has long been known to promote (if severe enough) systemic inflammation which can increase the risk for severe medical diseases, such as CVD, stroke, and arthritis [2,6]. However, to the best of our knowledge, the impact of periimplantitis on systemic inflammation has not yet been addressed in clinical (or animal) studies. Thus, the authors now propose that if systemic inflammation is demonstrated in patients with periimplantitis, then studies should be done to determine the efficacy, both locally in the mouth, and systemically in blood samples (to measure inflammatory diagnostic markers, such as highsensitivity C-reactive protein, interleukins, and prostanoids), of HMTs such as NON-antibiotic-dose doxycycline (“NAD” ie., Periostat®, Oracea®, both FDA-approved) and other HMTs, such as resveratrol [3,4] and curcumins [10-13]. In this regard, anecdotal observations in clinical practice (Joseph Bacigalupo, DDS, Garden City, NY), based on adjunctive treatment of patients with dental implants administered long-term NAD, indicated efficacy in reducing the incidence and severity of periimplantitis (Table 1). However, well-controlled double-blind placebo-controlled clinical trials are needed to (a) confirm this “clinical observation”, and (b) to scientifically determine whether systemic inflammation is a complication of periimplantitis, and is reduced or prevented by this HMT.

Patient No. Age (yr) Gender No. of implants/ duration Duration of HMT Prevented Pe.I. Reduced Pe.I. Pe.I. Currently: clinical radiographic evidence
#1 73 M 5/9 years † 6 years   None
#2 50 F 1/12 years † 4 years   None
#3 84 F 2/19 years † 17 years   None
#4 65 F 4/19 years † 3 years None
#5 62 M 1/11 years 3 years None

Table 1: Management of Periimplantitis (Pe.I.) by oral (systemic) host-modulation therapy† in a private practice.

Conflict of Interest

Lorne Golub is listed as an inventor on several patents on hostmodulation therapies and these have been fully assigned to his institution, The State University of New York at Stony Brook.


  1. Suzuki N, Yoneda M, Hirofuji T. Mixed red-complex bacterial infection in periodontitis. Int J Dent. 2013;587279.
  2. Golub LM, Lee HM. Periodontal Therapeutics: Current host-modulation agents and future directions. Periodontology. 2020;82(1):186-204.
  3. Ikeda E, Ikeda Y, Wang Y, Fine N, Sheikh Z, Viniegra A, et al. Resveratrol derivative-rich melinjo seed extract induces healing in a murine model of established periodontitis. J Periodontol 2018;89(5):586-595.
  4. Corrêa MG, Pires PR, Ribeiro FV, Pimentel SZ, Casarin RCV, Cirano FR, et al. Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. J Periodont Res. 2017;52(2):201-209.
  5. Meyer MS, Joshipura K, Giovannucci E, Michaud DS. A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control. 2008;19(9): 895–907.
  6. Graves DT, Ding Z, Yang Y. The impact of diabetes on periodontal diseases. Periodontology 2000. 2020;82(1):214-224.
  7. Salvi GE, Aglietta M, Eick S, Sculean A, Lang NP, Ramseier CA. Reversibility of experimental peri-implant mucositis compared with experimental gingivitis in humans. Clin Oral Implants Res. 2012;23(2):182-190.
  8. Xu L, Yu Z, Lee HM, Wolff MS, Golub LM, Sorsa T, et al. Characteristics of collagenase-2 from gingival crevicular fluid and peri-implant sulcular fluid in periodontitis and peri-implantitis patients: pilot study. Acta Odontolog Scand. 2008;66:219-224.
  9. Carcuac O, Berglundh T. Composition of human peri-implantitis and periodontitis lesions. J Dent Res. 2014;93(11):1083-1088.
  10. Elburki MS, Moore DD, Terezakis NG, Zhang Y, Lee HM, Johnson F, et al. A novel chemically-modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: Periodontal and Systemic effects. J Periodont Res. 2017;52(2):186-200.
  11. Elburki MS, Rossa Jr C, Guimarães-Stabili MR, Lee HM, Curylofo-Zotti FA, et al. A chemically modified curcumin (cmc 2.24) inhibits nuclear factor κb activation and inflammatory bone loss in murine models of lps-induced experimental periodontitis and diabetes-associated natural periodontitis. Inflammation. 2017;40(4):1436-1449.
  12. Sorsa T, Bacigalupo J, Könönen M, Pärnänen P and Räisänen IT. Host-modulation therapy and chair-side diagnostics in the treatment of peri-implantitis. Biosensors. 2020;10-44.
  13. Golub LM, Raisanen IT, Sorsa T, Preshaw P. An unexplored pharmacologic/diagnostic strategy for peri-implantitis: A protocol proposal. diagnostics. 2020;10(12)-1050.

Author Info

Lorne M. Golub*, Hsi-ming Lee and Stephen G. Walker
Department of Oral Biology and Pathology, Stony Brook, NY, USA

Citation: Golub LM, Lee H, Walker SG (2021) A Novel Concept to Promote the Health of Dental Implants: Host-Modulation Therapy. Int J Phys Med Rehabil. S5:002.

Received: 07-Apr-2021 Accepted: 21-Apr-2021 Published: 28-Apr-2021 , DOI: 10.35248/2329-9096.21.s5.002

Copyright: © 2021 Golub LM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.