MX2008007235A - Use of parathyroid hormone for treating periodontal and for other dental applications - Google Patents

Abstract

Method for treating or preventing periodontal disease associated with mild to severe alveolar bone loss, and for improving the prognosis of dental implant procedures by administering human parathyroid hormone to a patient in need thereof.

Description

USE OF PARATHYROID HORMONE FOR PERIODONTAL TREATMENT AND FOR OTHER DENTAL APPLICATIONS BACKGROUND OF THE INVENTION The present invention generally relates to the field of dental diseases and bone loss. More particularly, the invention relates to the therapeutic use of parathyroid hormone in the treatment of conditions associated with periodontal disease.

BRIEF DESCRIPTION OF THE INVENTION Periodontal disease in advanced stages is characterized by alveolar bone resorption, loss of soft tissue attachment, excessive tooth mobility and sometimes, loss of one or more teeth. It is the leading cause of dental loss in adults, affecting 50 million people in the United States alone. Only about 15% of individuals afflicted with periodontal disease are adequately treated. Periodontal disease has also been associated with an increased risk of heart disease and stroke, as well as premature infants of low birth weight, and therefore is an important health issue. The onset and progression of periodontal disease depends on the presence of specific types of bacteria in dental plaque, as well as the host response (inflammatory and immune) to these bacteria. Species of recognized bacteria associated with periodontal disease include Actinobacillus actinomycetemcomi tans and Porphyromonas gingivalis, both secrete a toxin that damages the surrounding tissues. The response of the host caused by the accumulation of dental plaque can also cause local tissue injury. As a result of this injury mediated by bacteria or host, the periodontal ligament is destroyed and continues with alveolar bone loss. Clinical signs of destruction include increased level of attachment and deep measurements that explore the pocket around the tooth, and radiographic evidence of local alveolar bone loss. Alveolar bone loss associated with periodontal disease not only increases the risk of loss of one or more teeth, but can prevent or challenge dental auxiliary replacement therapies that include dental implants. Current management of periodontal disease involves dental prophylaxis, incrustations and root programming, and in several cases, periodontal surgery may be necessary. Therapeutic agents to treat the disease include antiseptic agents and / or local / systemic antibiotics or microbial agents to control plaque causing plaque, and anti-inflammatory agents that reduce the inflammatory response of the host. While these methods may be effective in controlling or decreasing the progress of periodontal disease, limited alveolar bone is restored. Alveolar bone graft has been achieved with varying degrees of success using surgically implanted materials and topical agents, including bone grafts and bone morphogenetic proteins (BMPs). Regeneration of targeted tissue involves surgical placement of a membrane barrier between the bony defect and the superimposed soft tissue in an attempt to stimulate the formation of a new periodontal junction, as well as bone formation. The proportion of alveolar bone loss with periodontal disease is equally influenced by both local and systemic host factors. If the systemic bone loss as a result of osteopenia or osteoporosis also has detrimental effects on the alveolar bone has not been established. Systemic bone loss associated with osteoporosis can be treated with parathyroid hormone (PTH), which increases BDM and reduces the risk of vertebral and non-vertebral bone fracture. (R.M. Neer et al., NEJM, 19, 1434-1441, 2001). Since a need remains for a treatment of periodontal disease that restores alveolar bone loss, the present invention relates to administering parathyroid hormone (PTH) alone or in combination with one or more than other agents to humans or animals to restore alveolar bone associated with periodontal disease and also prevent bone loss. As a consequence of the alveolar bone graft, it is expected to improve the depth of the pocket probe and the level of clinical union. An objective of the present invention is to reverse alveolar bone loss including bone loss associated with periodontal disease by the administration of an effective amount of the parathyroid hormone to a patient in need thereof. Another objective of the invention is to induce new alveolar bone formation in a patient in need thereof by the administration of an effective amount of the parathyroid hormone. Yet another object of the invention is to increase the alveolar bone weight by administering an effective amount of the parathyroid hormone to a patient in need thereof. Yet another object of the invention is to increase the alveolar bone amplitude by administering an effective amount of the parathyroid hormone to a patient in need thereof. Another object of the invention is to increase the alveolar bone density by the administration of an effective amount of the parathyroid hormone to a patient in need thereof. Another objective is to decrease pocket depth depth and / or reduce the level of clinical attachment by administering an effective amount of the parathyroid hormone to a patient in need thereof. Yet another objective of the present invention is to reduce tooth mobility, by administering an effective amount of the parathyroid hormone to a patient in need thereof. A further objective of the present invention is to restore the alveolar bone that has been lost in the alveolar ridge after tooth extraction, by administering an adequate dose of the parathyroid hormone. Another objective of the present invention is to reduce the depth of pocket probe in a patient with periodontal disease by administering a suitable dose of parathyroid hormone. Another objective of the invention is to induce alveolar bone formation in a patient who suffers from or is about to undergo a dental implant procedure, with or without an auxiliary bone graft procedure, wherein the new alveolar bone formation provides additional support for a implant device, administering an adequate dose of parathyroid hormone. Another object of the invention is also to induce the bone formation in the alveolar vein in a patient who uses dentition, administering an adequate dose of parathyroid hormone. Yet another objective of the invention is to produce poor prognosis dental stability due to alveolar bone loss associated with periodontal disease, thereby reducing the risk of further tooth loss. These and other objects of the invention will be apparent to a person skilled in the art and the following detailed description of a preferred embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION The term "calculation" means a hard deposit of mineralized plate (also referred to as "tartar"). The term "osseointegration" generally refers to bone growth or adhesion on the surface of an implant, thereby blocking or stabilizing the implant in place. The term "pharmaceutically acceptable composition" means a formulation comprising PTH that is suitable for pharmaceutical use in humans. A composition can be in any form, such as a solution, suspension, freeze-dried pellet, oil, cream, tablet, capsule or ointment. Preferably, the composition it is in a ready-to-use, sterile solution form, for example, a ready-to-inject form. A PTH composition may be available for administration in any of a variety of containers, including a vial, bottle, jar, cartridge or pen-shaped injector device. The term "pharmaceutically acceptable carrier" means a solid or liquid chemical that is essentially pharmacologically inactive but is compatible with and suitable for pharmaceutical use in humans. Examples of pharmaceutically acceptable carriers include water, mannitol and lactose. A preferred carrier is water. The term "parathyroid hormone" means a full-length human parathyroid hormone ("PTH") 1-84, as well as biologically active fragments thereof including PTH (1-9), PTH (1-11), PTH (1-) 14), PTH (l-20), PTH (l-28), PTH (1-31), PTH (l-34), PTH (l-35), PTH (l-37), PTH (l-38) ), PTH (1-41) and PTH (1-64). The term also includes full-length PTH analogs or fragments thereof that include amino acid substitutions and derivatives. Such analogs may optionally comprise one or more polyethylene glycol (PEG) or Fe fragments. The term "pocket probe depth" (PPD) refers to the distance, measured in millimeters, from the periodontal pocket to the gingival margin (i.e. .

The term "clinical union level" (CAL) refers to the distance, measured in millimeters, from the cement-enamel junction (ie, crown margin) to the base of the pouch. Both PPD and CAL measurements are made with a periodontal probe at several sites around each tooth, for example the mesiobuccal or central buccal sites. They provide a measure of the severity of periodontal disease. The term "periodontal disease" as used herein means to encompass a spectrum of clinical conditions including 1) gingivial diseases that induce plaque or do not induce plaque, 2) chronic periodontitis, classified as light (1-2 mm CAL), moderate (3-4 mm CAL), or severe (> 5 mm CAL) of generalized or localized involvement, 3) aggressive periodontitis, classified as light (1-2 mm CAL), moderate (3-4 mm CAL) or severe (> 5 mm CAL) of generalized or localized involvement, 4) periodontitis as a manifestation of systemic diseases associated with hematological disorders, genetic or otherwise unspecified disorders, 5) necrotizing periodontal diseases including necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis , 6) abscesses of periodontium that includes gingival, periodontal and pericoronal abscesses, 7) periodontitis associated with endodontic lesions, and 8) development or acquisition of deformities and conditions, for example, factors related to the localized tooth that modify or predispose to gingival diseases or plaque-induced periodontitis, mucogingival deformities and conditions around the tooth, and conditions in the rib of the edentulous and occlusion trauma . All of these conditions can be located in one or a few teeth, or more generalized (ie,> 30% of sites are involved). The severity of the disease is usually based on the measured clinical union levels of the cement-enamel junction or crown margin, and can be considered medium (1-2 mm), moderate (3-4 mm) or severe ( > 5 mm). The severity of the disease may also be based on pocket depth depths, with median disease characterized by a pocket probe depth of approximately 4-5 mm, moderate disease characterized by a pocket probe depth of approximately 6-7. mm, and severe disease characterized by pocket probe depth of approximately = 8 mm.

Alveolar Bone Loss Alveolar bone loss is central to the pathogenesis of progressive periodontal disease. In some cases oral bone loss may occur together with systemic bone loss typically associated with osteopenia and osteoporosis. It is not clear whether it is a causal relationship between systemic bone loss and periodontal disease, or whether systemic bone density measurements are a sure predictor of mandibular bone density and / or risk of oral bone loss. Alveolar bone loss is influenced by multiple risk factors that include host-mediated immune responses to elevate cytokine levels associated with periodontal disease. Osteoclast activity associated with periodontal disease increases in the response mediated by the host.

Restoration of lost alveolar bone associated with periodontal disease The method of the present invention can be applied to animals or humans exhibiting vertical and / or horizontal alveolar bone loss, including bone loss associated with periodontal disease, with or without systemic bone loss associated with osteopenia or osteoporosis or other diseases of systemic bone loss. Patients having medium or severe alveolar bone loss can be treated by the method of the present invention to delay and / or prevent further loss of oral bone and to regenerate lost bone. The method of the invention increases the bone density, bone mass and bone strength of alveolar bone that has been weakened or destroyed, for example, during progress of periodontal disease or another degenerative disease. The application of the method of the invention decreases the risk of additional alveolar bone loss and stabilizes any remaining tooth, thereby reducing the risk of further tooth loss. The method of the invention can be applied, for example, to treat adult periodontitis in men and women, and the onset of periodontitis attack that affects young adults, adolescents and children, including prepubertal periodontitis. The method is also suitable for treating localized or generalized periodontitis, as well as rapidly progressive periodontitis. Juvenile forms of the disease are distinguished from forms of adult attack by attack age, and often by the proportion of disease progression and the types of bacteria associated with the disease. Certain patients may have a high risk of periodontal disease including post-menstrual women, diabetics, smokers and spheroid users. The method is also applicable to other forms of periodontal disease including disease associated with metabolic disorders such as diabetes mellitus, and hormonal alterations associated with, for example, menopause. The use of certain drugs such as anticonvulsants, calcium channel blockers and Cliclosporin may also increase the risk of gingival hyperplasia or periodontal disease, such as certain hematological disorders including disorders of the immune system caused by, for example, HIV. Periodontitis in adults is characterized by loss of clinical attachment due to destruction of the periodontal ligament, and loss of adjacent supporting bone tissue in otherwise healthy adults. Moderate periodontitis in adults is characterized by the loss of up to about 30% periodontal support tissue, while the disease in advanced or severe adult exhibits loss of more than 30% of periodontal tissue which can be detected, for example, by analysis radiographic Patients may experience periodontal destruction in a localized form, involving an area of a tooth or teeth, or the disease may be more general, involving multiple teeth or full dentition. Juvenile periodontitis may also be present in a localized or generalized form. The method of the present invention is suitable for treating various presentations of periodontal disease and for affecting one or more clinical benefits including reduction in the proportion of alveolar bone loss, reversal of alveolar bone loss, induction of alveolar bone formation, increase in mineral density oral bone (BMD), reduction of depth of pocket probe and level of clinical union, stabilization of teeth, reduction in the risk of dental loss and / or stabilization of dental implants. The method of the present invention can also be applied to patients having one or more diseases of independent or associated systemic bone loss such as, for example, osteoporosis and / or ostopenia, including drug-induced osteoporosis, eg, osteoporosis induced by spheroid. . The method of the present invention can also be applied to individuals which may have loss of one or more teeth, either through caries, trauma or periodontal disease, and which may also have surrounding bone loss. Bone loss in these areas may continue for a while. In some individuals, particularly in older individuals who may lose a number of teeth at a young age, they may have difficulty in using dentures, due to limited remaining bone support for the denture. This leads to problems with denture function and retention. The method of the invention can be used to help restore the rib in such cases and reduces the problems associated with the use of denture, where there is limited bone support.

Use with dental implants Another aspect of the present invention involves administration of the parathyroid hormone to increase alveolar bone mass in patients who have, or are about to have, a dental implant procedure. The method is particularly useful in patients who have inadequate alveolar bone to support an implant. Parathyroid hormone can be administered to accelerate the osseointegration of dental implants, thereby increasing the stability of dental implants. Patients with possible implant are examined by a dentist, periodontist or oral surgeon, and the implant procedures are carried out to replace a single tooth, several teeth or the entire upper or lower arch. Parathyroid hormone can be administered before or after an implant procedure. Patients with possible implant who have inadequate or insufficient alveolar bone mass or density for a successful implant procedure are administered with PTH for a period of about 1 month to about 6 months, preferably about 1 month to about 3 months, before a procedure of implant to form enough alveolar bone mass for the procedure. Parathyroid hormone can also be administered after a dental implant procedure to accelerate the osseointegration of an implant device, and / or to improve or increase the stability of an implant. The administration of PTH after implantation can be for approximately 3 months to approximately 12 months; preferably about 3 months to about 9 months; more preferably, about 3 months to about 6 months after an implant procedure. The invention also contemplates optionally administering PTH in conjunction with other treatments and / or procedures applied before, during, or after a dental implant procedure, including, for example, bone grafts, such as autografts, allografts, xenografts and alloplastic grafts and or administration of other bone active agents, such as, for example, bone growth factors, for example, BMPs, bone anti-osteo agents, for example, AMG-162, bisphosphonates, estrogen, SERM, calcitonin, cholecalciferol, vitamin D and calcium.

Administration of parathyroid hormone Parathyroid hormone can be administered parenterally or non-parenterally by any suitable route, including, for example, nasal, oral, buccal, pulmonary, intravenous, subcutaneous or intramuscular route, preferably, by subcutaneous injection. PTH can also be administered by local injection into the oral cavity, preferably in a site or socket in which bone loss has occurred. The parathyroid hormone can be formulated as a dry powder for nasal or pulmonary administration, freeze-dried formulations for reconstitution and injection, or ready to administer injectable solution formulations. Preferably, the formulation is a solution formulation ready for administration, for example, as described in US Patent 6,770,623, incorporated herein by reference. The stabilized solution formulations of the present invention may include a parenterally acceptable preservative. Suitable preservatives include, for example, cresols, benzyl alcohol, phenol, benzalkonium chloride, benzethonium chloride, chlorobutanol, phenylethyl alcohol, methyl paraben, propyl paraben, thimerosal and phenylmercuric nitrate and acetate. A preferred preservative is m-cresol or benzyl alcohol; the most preferred is m-cresol. The amount of preservative employed can vary from about 0.1 to about 2% by weight, preferably about 0.3 to about 1.0% by weight of the total solution. The parathyroid hormone compositions can, if desired, be provided in a powder form containing no more than 2% water by weight, after freeze drying of a sterile, aqueous hormone solution prepared by mixing sterilized forms of the selected parathyroid hormone, buffering agent or water, and a stabilizing agent as described above. Especially useful as a buffering agent when preparing lyophilized powders, it is a source of tartrate. Particularly useful stabilizing agents include glycine, sucrose, trehalose, mannitol, leucine, DPPC, and raffinose. Parathyroid hormone can also be formulated using any of the other suitable buffers and excipients to stabilize PTH. Pharmaceutical carriers and their formulations are described in Martin, "Remington's Pharmaceutical Sciences," 15th Ed .; Mack Publishing Co., Easton (1975). In one embodiment of the present invention, PTH is administered concurrently or sequentially with one or more other agents, drugs, vitamins and / or nutritional supplements. Suitable agents in accordance with this aspect of the invention include, inter alia, SERMS, raloxifene hydrochloride, calcitonin, bisphosphonates, growth factors, eg, bone morphogenetic proteins such as BMP-2, estrogen or bone marrow therapy. replacement of hormone, and calcium and / or vitamin D, the last two agents either through absorption of diet or by absorption of diet plus supplements. Preferably, the PTH administered according to the present invention is human PTH (1-34), although other fragments of PTH or full length hormone PTH (1-84) can be used. The parathyroid hormone is administered at a dose of about 5 μg to about 500 μg per day, more preferably about 5 μg to about 250 μg per day; 5 μg to approximately 100 μg / day, 10 μg to approximately 200 μg per day; 10 μg to approximately 100 μg per day; or about 10 μg to about 50 μg per day. More preferably, PTH (1-34) is administered at a dose of about 5 μg to about 50 μg per day; alternatively 15 μg to about 50 μg per day; 20 μg to 40 μg per day; or 20 μg to about 30 μg per day. Alternatively, PTH (1-34) can be administered daily at a dosage of about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 μg. Corresponding dosages of full-length PTH or PTH fragments other than PTH (1-34) are based on molar equivalents to PTH (1-34). Parathyroid hormone can be administered regularly (for example, once or more every day or week), intermittently (eg, irregularly for a day or week), or cyclically (eg, regularly for a period of days or weeks, followed by a period without administration). Preferably, PTH is administered once daily for 1-7 days for a period ranging from one month to 3 years. Alternatively, PTH can be administered for any period from 1 month to 2 years. More preferably, PTH is administered once daily for a period of 3 months to 2 years; more preferably, PTH is administered once daily for a period of 3 months up to 12 months. When PTH is co-administered with one or more active bone agents, such co-administration may be concurrent or sequential. Sequential treatment regimens include administration of bone active agents other than PTH over a period or periods in which PTH is not administered. By way of example, PTH can be administered regularly or intermittently for 6 months, followed by a period in which PTH is not administered, but some other active bone agent is administered. Co-administration of bone active agents other than PTH can occur before, or after a period in which PTH is administered, for about 1 month to 18 months; alternatively approximately 1 month up to 12 months; or about 1 month up to 6 months. Current treatments include, for example, regimens in which PTH is administered together with one or more other active bone agents at the same time, including on some days or alternate days within the same treatment period. Bone active agents other than PTH can be co-administered with PTH according to this aspect of the invention in any suitable dosage known to the person skilled in the art. For example, hormone replacement therapy (HRT) can be provided at dosages in the range of 0.5-1 mg of oral 17β-oestradiol, 25 μg of transdermal 17β-oestradiol, or 0.3 mg of conjugated equine estrogens. Bisphosphonates such as alendronate, and risedronate, can be administered at dosages in the range of 5-10 mg daily; calcitonin can be administered, for example, at 100-500 IU per day, and raloxifene at 20-200 mg per day; preferably 60-120 mg per day. These dosages are merely exemplary and other dosages known to the person skilled in the art can be used. One skilled in the art will recognize that the present invention can encompass numerous and varied treatment regimens, including PTH dosages, route and site of administration, specific PTH or fragment thereof, formulation, treatment period and, if appropriate , interval period between the days that include the administration of PTH and days without administration of PTH. Each treatment option can operate independently and can also be adjusted as needed to achieve the desired therapeutic goal. In one embodiment of the invention, a patient who has average periodontal disease and minimal alveolar bone loss, receives once daily, once every third day, or once weekly subcutaneous administration of PTH for a period of one month to twelve months. Patients who have moderate periodontal disease, can be treated by administration once daily, once every third day, or once weekly, of an adequate dose of PTH for a period of three months to twelve months, preferably six months to twelve months. Patients who have severe periodontal disease can be treated by administration once daily, once every third day, or once weekly, of an adequate dose of PTH for a period of three months to eight months, preferably six months to twelve months; more preferably, nine months to twelve months. While the preferred embodiments of the invention have been shown and described, it will be apparent to those skilled in the art, that various modifications may be made in these embodiments, without departing from the spirit of the present invention.

EXAMPLES Example 1. Treatment of a patient with periodontal disease before dental implant therapy A 65-year-old Caucasian male has a history of adult periodontitis. The patient has experienced significant alveolar bone loss radiographically confirmed, and has a number of tooth sites with deep measurements of pocket probes of approximately 7 mm. The patient has discussed with his dentist the possible severely affected tooth extraction and its replacement with dental implants, but the prospects for success are reduced in view of the bone loss that has occurred. Standard periodontal care is provided, including incrustations and root planning, and whose teeth with low prognosis are extracted. Before the implant surgery, the patient is administered with 20 μg of hPTH (1-34) once daily by subcutaneous injection for 3 months before implant surgery. After treatment with PTH, radiographic analyzes reveal increased alveolar BMD and reduced pocket probe depth around remaining dental. No complications occur after implant replacement.

Example 2. Treatment of a patient with moderate to severe periodontal disease A post-menopausal 75-year-old woman without osteoporosis or any other condition of systemic bone loss is presented for tooth extraction. The patient has a long history of chronic and severe gum bleeding, associated with chronic gingivitis but is otherwise in good health. Clinical examination and radiographic analysis showed significant alveolar bone loss, and deep measurements of pocket probes, and a diagnosis of severe periodontal disease is made. The patient receives standard periodontal treatment that includes incrustation and root planning, with surgery if necessary, and self-injects 15 μg once a day of hPTH (1-34) subcutaneously for 12 months. Based on restricted diet habits, the patient is advised to take calcium and vitamin D supplement daily. Deep pocket tube measurements are taken every three months for a period of 12 months. At the end of the 12-month period, the patient exhibits reduced pocket probe depth and radiographic analysis reveals restoration of alveolar bone loss.

Example 3. PTH administration (1-34), reduces depth of probe in a patient with onset of adult periodontal disease A 40-year-old male smoker presents aggressive periodontal disease. The patient has already incurred several extractions of teeth and there is evidence of advanced alveolar bone loss that threatens the remaining teeth. The patient receives intense periodontal treatment that includes root encrustation and planning and begins subcutaneous injections of hPTH (1-34) once daily at a dose of 30 μg per day. Pocket depths are measured at regular intervals during a 12-month treatment period. After 12 months, the patient shows marked improvement, with some sites exhibiting deep abnormal spacing.

Example 4. Administration of PTH to repair bone defects associated with early onset periodontitis A 25-year-old woman presents with early onset periodontitis, characterized by advanced bone loss, which includes vertical interproximal defects and involvement in the form of a molar fork. It also exhibits increased tooth mobility and anterior incisor tooth deviation. Along with the intense periodontal treatment, which includes incrustation and root planning, human PTH (1-34) was administered at a dose of 30 μg per day by subcutaneous injection, together with debridement to repair bone defects. After 6 months of treatment, the patient exhibits dental stabilization.

Example 5. Dental Implant Applications A 55-year-old woman presents with advanced oral bone loss as a result of periodontal disease and already has multiple tooth loss. She is interested in saving her remaining tooth and replacing those that have been lost with implants as soon as possible. It is treated with hPTH (1-34) at a dosage of 25 μg once daily by subcutaneous injection, together with debridement. Three months after the start of treatment with PTH (1-34), the patient receives implants and continues to receive PTH for 3 additional months after the procedure. The implants are stabilized and functional within 3 months of placement. The woman retains her remaining tooth for 24 months of additional observation.

Example 6. Treatment of Early Onset Periodontal Disease A 15-year-old girl shows that she already has severe tooth loss due to aggressive juvenile periodontal disease. The radiographic analysis shows significant alveolar bone loss. The girl receives intense periodontal treatment and is subsequently treated for 3 months with PTH (1-34) given three times a week at a dose of 10 μg per day by subcutaneous injection, followed by an additional 3 months with daily injection at a dose of 20 μg per day. The girl it presents improvement in its achieved clinical levels and interior bone filling around affected dental. No more teeth are lost during follow-up. Dental implants are used to successfully replace tooth loss due to periodontal disease.

Claims (20)

1. A method for the treatment of periodontal disease in a human patient, characterized in that it comprises the administration of human parathyroid hormone in a daily dose of 5 μg to 250 μg, where the treatment restores the alveolar bone loss.

2. A method according to claim 1, characterized in that the treatment reduces the bone loss associated with periodontal disease.

3. A method according to claim 1, characterized in that the treatment restores alveolar bone loss in one or more affected dental cavities after tooth extraction.

4. A method according to claim 1 or 2, characterized in that the treatment reduces the depth of pocket probe.

5. A method according to claim 1 or 2, characterized in that the treatment increases the alveolar BDM.

6. A method according to claim 1, characterized in that the periodontal disease is selected from the group consisting of juvenile periodontitis, periodontitis in adult, gingivo-necrotizing ulcerative periodontitis, refractory periodontitis, periodontitis of early attack, aggressive periodontitis and periodontitis associated with systemic disease.

7. A method according to claim 6, characterized in that the periodontal disease is moderate, moderate or severe periodontal disease. A method according to claim 1, characterized in that the treatment further comprises co-administering an agent selected from the group consisting of vitamin D, calcium, estrogen, hormone replacement therapy, bisphosphonate, calcitonin and SERM. 9. A method according to claim 1, characterized in that the treatment with parathyroid hormone is for a period of one month up to 24 months, and where at the end of the treatment period one or more other agents are administered, selected from the group consisting of vitamin D, calcium, estrogen, hormone replacement therapy, calcitonin, bisphosphonate and SERM. A method according to claim 1, characterized in that the parathyroid hormone is selected from the group consisting of PTH (1-28), PTH (1-31), PTH (1-34), PTH (1-37). , PTH (1-38), PTH (1-41) and PTH (1-84). 11. A method according to claim 1, characterized in that the parathyroid hormone is administered parenterally. 12. A method in accordance with the claim 1, characterized in that the parathyroid hormone is PTH (1-34) and the daily dose is 5 μg to 50 μg. 13. A method according to claim 1, characterized in that the treatment increases bone mass. 14. A method according to claim 1, characterized in that the treatment improves the bone structure. 15. A method according to claim 1, characterized in that the treatment stabilizes one or more teeth. 16. A method in accordance with the claim 1, characterized in that the treatment reduces the additional bone loss in the dental cavity. 17. A method in accordance with the claim 2, characterized in that the depth of the pocket probe is restored to normal. 1

8. A method according to claim 1, characterized in that the parathyroid hormone is administered by local injection in or near the dental cavity. 1

9. A method for improving the prognosis of a dental implant procedure in a patient having inadequate alveolar bone mass, characterized in that it comprises administering human parathyroid hormone to the patient in a daily dose of 5 μg to 250 μg for a period of approximately 3 months to approximately 6 months before the procedure. 20. A method for accelerating the osseointegration of a dental implant in a patient after placing an implant, characterized in that it comprises administration of human parathyroid hormone at a daily dose of 5 μg to 250 μg.