Periodontal management in Paget's disease: Case presentation and a brief review of literature.

Paget's disease of bone is a common condition characterized by increased and disorganized bone turnover which can affect one or several bones throughout the skeleton. These abnormalities disrupt normal bone architecture and lead to various complications such as bone pain, osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors and environmental factors like paramyxovirus infection have been implicated in etiology. This is a case report of a patient who presented with Paget's disease and the periodontal surgical management, after the pretreatment was employed with diagnostic procedures like computed tomography and serum alkaline phosphatase tests.

INTRODUCTION

Paget's disease of bone is a form of osteodystrophy characterized by disorganized formation and remodeling of bone, unrelated to functional requirements. It is the second most common bone disease after osteoporosis (Kanis, J.A.).[1] The disease is characterized by focal regions of highly exaggerated bone remodeling, with abnormalities in all phases of the remodeling process. The etiology of the disease remains unclear, but it is thought to be due to a primary dysfunction of osteoclasts (Parfitt, A.M.).[2]

Paget's disease is an autosomal dominant trait with genetic heterogeneity. Recurrent mutations in the ubiquitin associated domain of sequestosome 1 (SQSTM1/p62) are identified in patients with Paget's disease. Following childhood infection with paramyxoviruses, such as measles or respiratory synctial virus, they may remain latent in osteoclast progenitor cells; this latent infection is implicated as an etiological basis (Roodman GD).[3] However, a cause and effect relationship for the paramyxoviral infection and SQSTM1/p62 gene mutations associated with this disease and osteoclast abnormalities are unclear (Najat et al.)[4]

According to Reddy SV,[5] osteoclasts and osteoclast precursors from patients with Paget's disease containing paramyxoviral transcripts appear hyper-responsive to 1,25-(OH)2D3 and and Receptor activator of nuclear factor Kappa-B ligand (RANKL). This hyper-responsiveness of osteoclast precursors in Paget's disease results from increased expression of co-activators of vitamin D receptor. Gene polymorphisms and enhanced levels of cytokine/growth factors associated with Paget's disease have been observed. The enhanced production of IL-6 by osteoclasts, which can be autocrine/paracrine in Paget's disease, may further amplify the increased osteoclast formation already ongoing in pagetic lesions. Since osteoclast and osteoblast activity remain coupled in Paget's disease, the increased osteoclast activity would result in increased osteoblast numbers which rapidly deposits new bone in a chaotic fashion, so that the bone formed in pagetic lesions is of poor quality and is disorganized rather than lamellar in character. As more and more bone is formed, the lesion would eventually become sclerotic. The increased numbers of immature osteoblasts expressing high levels of RANKL and Macrophage-colony stimulating factor (M-CSF) would further increase osteoclast formation (Horwood et al.).[6]

Recent studies have shown that the estrogen alpha receptor (ERα) and calcium sensing receptor gene (CaSR) polymorphisms may contribute to genetic susceptibility to Paget's disease. Estrogen appears to play a crucial role in immunological events, including its inhibitory effect on IL-6 secretion, and also, calcium sensing receptor gene, (CaSR), has a crucial role in the regulation of extracellular calcium that might be of importance at the site of pagetic changes in bone (Donáth et al.).[7]

Signs and symptoms

Hearing loss: Due to temporal bone involvement.

Nerve root compression: Impingement of nerve root by increased bone formation.

Headache: Due to skull being affected by Paget's disease.

Bone pain: Usually results from osteoarthritis in joints adjacent to pagetic bones.

Bone deformities: Due to rapid formation of poor-quality bone it can result in bowing of a limb or increased skull size.

Fracture: Bone in pagetic lesions is weaker than normal bone and can develop characteristic “chalk stick-like” fractures.

Inclusion body myopathy: Preferential involvement of distal muscles in the lower extremities, especially the anterior compartment of the legs, with relative preservation of the quadriceps due to bony enlargement (Ju et al.).[8]

Frontotemporal dementia: Degeneration of the frontal lobe and temporal lobes of the brain due to enlargement of the skull (Ju et al.).[8]

Congestive heart failure: Due to chronic severe anemia, large arteriovenous fistula or multiple small arteriovenous shunts (Anand IS, Florea VG).[9]

CASE REPORT

A female patient of 39 years, reported to the Department of Periodontics, Thai Moogambigai dental College and Hospital, Chennai. Her Chief Complaint was pain in the upper right posterior teeth.

When the patient was examined extra-orally, there was asymmetry in the facial appearance [Figures 1–3]. The circumference of the head was increased in the occipital region. When intra-oral examination was done, there was spacing present between the teeth and there was bony prominence on the right side of the palate till the mid palatine region [Figure 4]. While recording the history, the patient mentioned that the circumference of the head gradually increased for the past 10 years; there was also gradual increase in spacing between the teeth [Figures 5 and 6] since her paget's disease was diagnosed, which could be due to the increase in the size of the jaws. Periodontal examination was done using William's probe and pocket depth was measured at six sites per teeth. Seven millimeter pocket was observed locally, in the regions 16 and 17 [Figure 7].

Figure 1

Right profile view

Figure 3

Enlargement of the nasal process of maxilla

Figure 4

Bony enlargement of the palate

Figure 5

Spacing between the teeth in the 1st and 4th quadarant

Figure 6

Spacing between the teeth in the 3rdquadarant

Figure 7

Preoperative pocket measurements in 16 and 17 regions

Left profile view

Investigations

The initial phase of Paget's disease is characterized by excessive bone resorption in a focal region; the radiological examination in the early stages of the disease frequently shows an osteolytic lesion. Subsequently, bone formation is markedly increased, with increased numbers of osteoblasts that appear hyperactive resulting in a cotton wool appearance. Radiographic investigations were carried out using orthopantomogram (OPG), intra oral periapical (IOPA), and computed tomography (CT) scan.[10] OPG revealed hypercementosis in the teeth 14 and 15 [Figure 8]. IOPA revealed horizontal bone loss in relation to 16 and 17 regions. CT scan was done to observe any pathology in the oral cavity which could determine the outcome of periodontal treatment and prosthetic replacement of 46 and 36 teeth. CT scan revealed the presence of woven bone or immature bone by observing the radio density in the occipital region, palate, and mandible that correlated the clinical findings [Figures 9–11]. Laboratory investigations were done for detecting the levels of serum alkaline phosphatase levels which was 1600 IU/ml.

Figure 8

OPG showing hypercementosis in 14 and 15 regions

Figure 9

Saggital section of CT scan showing growth in the intercorticol spaces of saggital and occipital bones

Figure 11

Saggital section of CT scan showing pockets being measured using software

Cross sectional view of CT scan showing growth in the intercorticol spaces of maxilla and occipital bones

Treatment

The treatment was done for the patient, which consisted of emergency endodontic therapy as the patient had pain in the regions 16 and 17 due to deep carious lesion. Phase I therapy where routine scaling and root planing was done and oral hygiene instructions were given. After one month, reevaluation of the patient was done, she appeared to be adhering to the oral hygiene instructions, but still there was a pocket of 6 mm present in the interdental regions of 16 and 17. So phase II or surgical phase therapy was carried out for the patient, which consisted of flap surgery in the areas 16 and 17 [Figures 12 and 13]. The treatment was uneventful with healing without complications, and after one week, the sutures were removed [Figure 14].

Figure 12

Horizontal bone loss in 16 and 17 regions

Figure 13

Flap closure with black silk

Figure 14

Postoperative view of 16 and 17 regions

Spaces were closed using composite restorations in the anterior regions for esthetic reasons. Since it is a progressive disease, patient will be followed and further treatment may be planned as required.

DISCUSSION

Certain treatment considerations have to be taken into account in a Paget's disease case which consists of proper clinical and radiographic examination along with biochemical tests, which are calcium profile, serum alkaline phosphatase (SAP), CTX (Cterminal cross linked telopeptide), and NTX (N terminal cross linked telopeptide). Calcium levels are usually normal in Paget's disease which was also seen in our case. Levels of SAP and urinary Nterminal telopeptide of type I collagen are used to monitor therapy. SAP levels in our case were 1,600 IU/ml initially, and later with Zolandronic acid therapy was brought under 300 IU/ml.

Alveolar bone loss in periodontitis and skeletal bone loss share common mechanisms (Palomo et al.).[11] Bisphosphonates are in wide use to treat this condition and alveolar bone loss, but with negative side effect of osteonecrosis of the jaw (BRONJ).

The cancellous bone is replaced by osteoid or woven bone which is immature and may have increased vascularity (Kannan et al.).[12] In our case, we could find bone loss clinically and radiographically only in a localized area as opposed to the findings normally seen in a Paget's disease case, which could be due to good oral hygiene of the patient and bisphosphonate therapy. But due to increase in the jaw size, there can be pathologic migration leading to food impaction and localized bone loss.

Prosthetic replacement of edentulous spaces in 36 and 46 regions was considered using implant supported crowns; but as there was high vascularity and lower density of bone, it was considered inappropriate to carry out the implant placement, because primary stability would have been compromised and operative complications would arise that would be detrimental on implant success. But according to Grant et al.[13] who reported a case series which consisted of 115 patients undergoing bisphosphonate therapy and were treated successfully with dental implants, and in another case report by Torres et al.[14] there was successful implant placement done in a Paget's disease case who was under bisphosphonate therapy. There are case reports by Bedogni et al.[15] and Shin et al.[16] suggesting to be cautious when placing implants or osteotomy being done to the patients who have osteoporotic bone and who are on long term bisphosphonate therapy, because there could be compromised healing. These patients were successfully treated with systemic antibiotics, local microbial mouth rinse and aggressive defect management (detoxification and mixture of bone graft and tetracycline). Secondary placement of implants was also reported in few cases that were under bisphosphonate therapy (Pirih et al.).[17]

CONCLUSION

Although patient with Paget's disease of the bone present with certain degree of challenge, pretreatment investigations will give a clear picture and reduce the complications both operative and postoperative. The presence of increased spacing between teeth which is dynamic, vascularity in the immature bone and the osteonecrosis after a bisphosphonate therapy does throw a greater challenge to a periodontist in managing the periodontal condition of the patients with Paget's disease.