Dental Implants in Patients With X-linked Hypophosphatemia (IMPLANTS-XLH)

X-linked hypophosphatemia (XLH) is a rare genetic skeletal disease where increased phosphate wasting in the kidney leads to hypophosphatemia and prevents normal mineralization of bone and dentin, with osteomalacia as a principal manifestation. In previous works, the investigators have shown that adults with XLH present with more frequent and severe periodontitis than in the general population, and that vitamin D and phosphate supplementation improves their periodontal health, as it does for the osteomalacia. Their medical records also reveal that early implant failure is dramatically increased in these patients, when no supplementation is implemented, and standard surgical protocols followed. In contrast, the investigator's preliminary data showed that successful osseointegration was achieved with supplementation prior and after implant placement and extended healing time. Here, the investigators propose to assess the current recommendations for implant therapy in XLH patients, with 24 implants placed. The current recommendations consist of: 1) supplementation with vitamin D and phosphate for 3 months prior to implant placement and 6 months after; 2) implant healing time extended to 6 months. If osseointegration is achieved, prosthesis will be fabricated. Radiographic and clinical examination at 6, 12, 18 and 24 months after placement of the definitive restoration will evaluate the implant osseointegration, crestal bone level and peri-implant tissues health.

Study Overview

• Status: Recruiting
• Conditions: X-linked Hypophosphatemia
• Intervention / Treatment: Procedure: Dental Implant placement

Detailed Description

Primary objective: to evaluate the efficacy of the specific implant management currently offered to XLH patients according to the recommendations, in terms of implant survival.

Secondary objectives: 1. to study the evolution of the peri-implant bone level within 2 years after implant placement ; 2. to study the evolution of the stability of the peri-implant tissues in the 2 years following the installation of the implant ; 3. to describe the osseointegration of the implant 6 months after insertion ; 4. to evaluate the effectiveness of the specific implant management in terms of the delay in occurrence of the first implant loss of patients ; 5. to describe the reasons for removal of the implants ; 6. to evaluate the satisfaction of the implant treated patient ; 7. to describe the occurrence of dental plaque, suppuration or bleeding around implants.

Experimental plan: this is an observational prospective study with historical control group (retrospective compendium) comparing XLH-specific implant management (prior phosphorus / vitamin D supplementation and prolonged implant healing) to non-specific management. For prospective inclusion (patients with specific implant management) patients will be recruited from adults with XLH as part of an oral assessment. After inclusion each patient will be followed 24 months. The surgical treatment and the clinical and radiographic follow-up correspond to the specific management proposed in our service to the patients presenting an XLH. Prior to implant placement, a cone-beam computed tomography scan will confirm adequate bone volume for implant placement. Implant surgery will be performed under local anesthesia following the protocols recommended by the manufacturer. The follow-up is done during the healing period and the realization of the implant prosthesis (6 months after surgery) then 12, 18 and 24 months after the surgery. It will include a clinical and radiographic examination, and will verify the presence of the implant in the mouth (survival of the implant), and the stability of the peri-implant tissues (level of attachment and bone level)

• Study Type: Observational
• Enrollment (Anticipated): 36

Contacts and Locations

• Study Contact: Name: Martin Biosse Duplan, DDS, PhD; Phone Number: +33 1 53 11 14 15; Email: martin.biosse-duplan@aphp.fr

Study Locations

• France
  • Paris, France, 75018
    • Recruiting
    • Service d'Odontologie - Hôpital Bretonneau - 23 rue Joseph de Maistre
    • Contact: Martin Biosse Duplan, DDS, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with X-linked hypophosphatemia

Description

Prospective patients:

Inclusion criteria

• Man or woman
• 18 years of age or older at the time of inclusion
• Diagnosis of X-linked hypophosphatemia confirmed by an endocrinologist or a rheumatologist
• Supplemented with phosphate and vitamin D for a period of at least 3 months
• Presenting an indication of a simple implant treatment (healed implant site with adequate bone volume) with rehabilitation using a single or partial fixed prosthesis
• Affiliated to the national social security assurance

Exclusion Criteria:

• Opposition to participation in research
• Presence of other uncontrolled diseases that may have an impact on the periodontium (eg diabetes or chronic kidney disease)
• Contraindications to implant treatment, such as active periodontitis and heavy smoking (more than 10 cigarettes per day)
• Patient under guardianship or trusteeship.

Retrospective control patients:

The data will be collected retrospectively for patients who meet the following criteria:

• Man or woman
• Aged 18 years or older at the time of implant treatment
• Diagnosis of X-linked hypophosphatemia confirmed by an endocrinologist or a rheumatologist
• Having had non-specific XLH implant treatment (absence of phosphate / vitamin D supplementation and / or absence of prolonged healing)
• Non opposition to the use of the data of care collected as part of the research
• Absence at the time of implant treatment of uncontrolled diseases that may have had an impact on the periodontium (diabetes, chronic kidney disease, smoking > 10 cigarettes per day)
• Not under guardianship or trusteeship.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective Dental Implant placement; Patients prospectively included and treated following current recommendations	Procedure: Dental Implant placement; Surgical placement of dental implant not associated with prior or concurrent bone augmentation
Retrospective Dental Implant placement; Patients retrospectively included, that did not benefit from current recommendations	Procedure: Dental Implant placement; Surgical placement of dental implant not associated with prior or concurrent bone augmentation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implant loss	Loss of the dental implant within 24 months after placement, defined by the absence of the implant in the mouth objectified during a clinical examination (spontaneous loss) or by the removal of the implant whatever the cause	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peri-implant bone level	Peri-implant bone level measured on dental x-rays	24 months
Clinical attachment level	Clinical attachment level, calculated from the pocket depth and gingival level measures and measured with a periodontal probe	24 months
Lack of mobility of the implant	Lack of mobility of the implant	6 months
Time of onset of the first implant loss	Time of onset of the first implant loss	24 months
Cause of removal of the implant	Cause of removal of the implant	24 months
Satisfaction of the treated patient	Satisfaction (or not) of the treated patient	24 months
Presence of dental plaque, suppuration or bleeding at the level of the implant	Presence of dental plaque, suppuration or bleeding at the level of the implant	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Martin Biosse Duplan, DDS, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: dental implants; osseointegration; hypophosphatemia; hypophosphatemic rickets
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Rickets; Vitamin D Deficiency; Rickets, Hypophosphatemic; Hypophosphatemia, Familial; Familial Hypophosphatemic Rickets; Hypophosphatemia
• Other Study ID Numbers: HAO 018045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No