This document provides an overview of bisphosphonates. It discusses their history, structure, indications, mechanisms of action, roles in periodontal therapy, side effects including BRONJ (bisphosphonate-related osteonecrosis of the jaw), and dental management considerations for patients receiving oral bisphosphonate therapy. The document covers bisphosphonates' effects at the tissue, cellular, and molecular levels and reviews both animal and human studies on their use in periodontal applications. It also addresses their potential analgesic properties and optimal duration of use.

1. “BISPHOSPHONATES”
Under the esteemed guidance of ;-
Prof. Dr. SUHAIL MAJID JAN
(HOD / Guide)
Dr. ROOBAL BEHAL
(Associate Prof & Co-Guide)
Presented By:-
MOHAMMAD IMRAN BHATT
PG (2nd Year)
‘’POST GRADUATE DEPARTMENT OF PERIODONTICS ANDORAL
IMPLANTOLOGY’’

2. CONTENTS
• INTRODUCTION
• HISTORY
• STRUCTURE OF BISPHOSPHONATES
• INDICATIONS
• BIOAVAILABILITY, PHARMACOKINETICS
• HOW TO TAKE BISPHOSHONATES
• CLASSIFICATION
• MECHANISM OF ACTION
• ROLE IN PERIODONTAL THERAPY
• SIDE EFFECTS
• BRONJ
• DENTAL MANAGEMENT OF PATIENTS RECEIVING ORAL
BISPHOSPHONATE THERAPY
• REFERENCES

3. HISTORY
• Designed as synthetic ( Non-biodegradable)analogues of
pyrophosphate.
• Initially used in industry as water softening agents in
irrigation systems in the earlier 1920s. After that the medical
use of the bisphosphonates came into existence.
• Etidronate, first bisphosphonate for medical use.
• In 1969, bisphosphonates discovered as bone loss inhibitors.
• Initial launch of Fosamax (alendronate) by Merck & Co.
( 1990)

4. • blocks precipitation of calcium phosphate in
plasma, urine, and soft tissues.
• commonly used as an anti-tartar agent in
toothpaste.

5. STRUCTU
RE

7. The long side-chain (R2 in the diagram)
determines the chemical properties, the
mode of action and the strength of
bisphosphonate drugs. The short side-
chain (R1), often called the 'hook', mainly
influences chemical properties and
pharmacokinetics.

8. Etidronate
Clodronate
Tiludronate
Pamidronate
Alendronate
Risedronate
Ibandronate
Zoledronate

9. INDICATIONS

10. FDA APPROVED
INDICATIONS
• 1. Osteoporosis
• 2. Paget’s disease
• 3. Malignant hypercalcemia
• 4. Bone metastasis
• 5. Multiple myeloma,
• 6. Primary hyperparathyroidism,
• 7. Osteogenesis imperfecta and
• 8. Carcinoma of breast.

11. Their use also has been proposed in the management
of periodontal diseases,
Bisphosphonates inhibit the osteoclastic bone
resorption & hence are used as a host modulating
factor for prevention of bone loss.
(Parfitt AM. Journal of Cell Biochemistry 1994;
55(3):273–286.)

12. Treatment concept that aims to reduce tissue
destruction and stabilize or even regenerate the
periodontium by modifying or downregulating
destructive aspects of host response and
upregulating protective or regenerative
responses. (CARRANZA)

13. .
Systemically
Administered
Agents :-
 NSAIDs
Bisphosphonate
s
Subantimicrobi
al-
Dose
Doxycycline
 Locally
administered
Agents :-
 Topical NSAIDs
 Enamel matrix
proteins
 Growth factors
 Bone
morphogenetic
proteins
Host modulating agents

14. Bisphosphonates also
possess anti-collagenase
properties
( Nakaya, 2000)

15. BIO-AVAILIBILITY
• Chemical adsorption onto hydroxyapatite
• Cellular uptake by osteoclasts, macrophages, tumor
cells, etc
• Less than 1% of the oral dose absorbed
• GI absorption suppressed by food intake
• For a more rapid and effective action,
bisphosphosphonates can be given by IV infusion.

16. PHARMACOKINETICS
• transient distribution to liver and other organs
• as a sponge, metabolically active bone adsorbs IV dose
• pharmacokinetics is complex; bisphosphonates remain
attached to bone for weeks to months
• amount of drug released in plasma related to rate of
bone metabolism and turnover

17. HOW TO TAKE
BISPHOSPHONATES?

18. • Usually takes between 6-12 months for
bisphosphonates to work, and they are normally taken
for at least five years (some people take them for much
longer).
• Always taken with a full glass of water on an empty
stomach, and you must stand or sit upright for 30
minutes after you take them.
• Wait between 30 minutes and 2 hours before you eat
any food or have any other drinks.
• Most people are given calcium and vitamin D to take (at
a different time to the bisphosphonate) when they are

19. CLASSIFICATION

20. • According to chemical structure:-
 1. Alkyl side chains ( Etridonate )
2. Amino side chains (Alendronate )
3. Cyclic chains (Zelandronate )
• They can also be classified as:
1. Nitrogenous compounds which include
Pamidronate, neridronate, Olpadronate
2. Non-nitrogenous compounds which include
Etidronate, Clodronate, Tiludronate.

21. • The non-nitrogenous
bisphosphonates(disphosphonates) are metabolised in
the cell to compounds that replace the terminal
pyrophosphate moiety of ATP, forming a non-
functional molecule that competes with adenosine
triphosphate(ATP) in the cellular energy metabolism.
The osteoclast initiates apoptosis and dies, leading to
an overall decrease in the breakdown of bone
• Nitrogenous bisphosphonates act on bone metabolism
by binding and blocking the enzyme farnesyl
diphosphate synthase (FPPS) in the HMG-CoA
reductase pathway (also known as the mevalonate
pathway)

23. • Disruption of the HMG CoA-reductase pathway at the
level of FPPS prevents the formation of two metabolites
(farnesol and geranylgeraniol) that are essential for
connecting some small proteins to the cell membrane.
This phenomenon is known as prenylation, and is
important for proper sub-cellular protein trafficking .
• While inhibition of protein prenylation may affect many
proteins found in an osteoclast, disruption to the lipid
modification of Ras, Rho, Rac proteins has been
speculated to underlie the effects of bisphosphonates.
These proteins can affect both osteoclastogenesis, cell
survival, and cytoskeletal dynamics. In particular, the
cytoskeleton is vital for maintaining the "ruffled
border" that is required for contact between a
resorbing osteoclast and a bone surface

24. Drug name/Trade name(s) Route of administration
Nitrogen containing
 Alendronic acid (Fosamax) Oral
yes
Disodium Etidronate (Didronel) Oral
no
Disodium pamidronate (Aredia) IV
yes
 Ibandronic acid(Bondronat) Oral/IV
yes
 Risedronate sodium (Actonel) Oral
yes
 Sodium Clodronate (Loron) Oral/IV
no

25. MECHANISM OF ACTION

26. MECHANISM OF ACTION AT VARIOUS
LEVELS
A) Tissue level
Decrease bone turnover due to decrease bone
resorption.
Decrease number of new bone multicellular units.
Net positive whole body bone balance.
B) Cellular level
Decrease osteoclast recruitment (Rodan et al.,
Strewler)
Increase osteoclast apoptosis (Hughes et al., Rogers
et al.)
Decrease osteoclast adhesion
Decrease depth of resorption site
Decrease release of cytokines by macrophages
Increase osteoblasts differentiation and number.

27. C) Molecular level
Inhibits mevalonate pathway (can result in
perturbed cell and induction of apoptosis).
Decrease post-transitional prenylation of GTP
blinding proteins.
(International Journal of Applied Biology and Pharmaceutical
Technology,Volume 3, issue -3, pages 103-108, July- Sept
2012)

30. A bisphosphonate group mimics pyrophosphate’s
structure, thereby inhibiting activation of enzymes that
utilize pyrophosphate. Bisphosphonate-based drugs’
specificity comes from the two phosphonate groups (and
possibly a hydroxyl at R1) that work together to
coordinate calcium ions.
Bisphosphonate molecules thus bind preferentially to
calcium, and bones being the largest source of calcium in
body, accumulates maximum bisphosphonate molecules.
Bisphosphonates, when attached to bone tissue, are taken
up by osteoclasts.

31. Bisphosphonates affect both bone resorption and
deposition by various mechanisms.
• 1. They bind to hydroxyappatite thus preventing its
dissolution.
• 2. They inhibit osteoclast activation thus reducing
the rate of bone resorption.
• 3. They increase osteoblast differentiation thus
aiding in bone formation.
• 4. Their anti- collagenase activity prevents
degradation of the organic components of bone.

33. These actions of bisphosphonates have made them
highly popular for the management of bone metabolic
diseases like osteoporosis and other bone resorptive
conditions like Paget’s disease and malignant
hypercalcemia.
It is this bone sparing property of bisphosphonates
that has attracted Periodontists towards the use of
these drugs for prevention of alveolar bone loss that
occurs in periodontal disease, thus opening a new
chapter in periodontal host modulation therapy.

34. ROLE IN PERIODONTAL THERAPY

35. Early 1990’s saw an increasing interest in
application of bisphosphonates as host modulating
agents for the treatment of periodontal disease.
Many animal studies proved the high clinical
efficacy of bisphosphonates in inhibiting the
progression of experimentally induced
periodontitis. These improvements in periodontal
clinical parameters, especially alveolar bone gain,
were also achieved in many human clinical trials.

36. ANIMAL STUDIES:
BP USED, ADMINISTRATION ,EFFECT ON BONE
RESORPTION, EFFECT ON PERIODONTAL HEALING
• Reddy et al (1995), Alendronate oral route, ↓alveolar bone
resorption, ↑Bone mass
No clinical effect on clinical parameters
• Alencar et al ( 2002), Chlondronate Subcutaneous route,
↓alveolar bone resorption & osteoclast, ↓PMNs
• Buduneli et al (2004), Alendronate Intravenous route,
↓alveolar bone resorption, ↑Serum osteocalcin

37. HUMAN STUDIES:
BP USED, ADMINISTRATION ,EFFECT ON BONE
RESORPTION, EFFECT ON PERIODONTAL HEALING
• Rocha et al (2001), Alendronate oral route, ↓alveolar bone
resorption, ↓Tooth mobility, ↓In clinical parameters
• Lane et al (2005), Alendronate OR Residronate oral route,
No effect on periodontal bone mass, ↓Pocket probing
depth, bop and clinical attachment level
• Takaishi et al (2003), Etridonate oral route ,↑alveolar
bone deposition, ↓Pocket probing depth and mobility

38. LOCAL DRUG
ADMINISTRATION
• YAFFE A et al (2003) found that in local drug
delivery of tetracycline in combination with
alendronate showed significant reduction in
alveolar bone loss.
• A R PRADEEP et al (2012) in two different studies
found significant reduction in PD and CAL and also
more percentage of bone fill after using 1 % of
Alendronate gel in the treatment of both chronic
as well as aggressive periodontitis.

39. • A Yaffe et al, Alendronate Local drug delivery with
tetracycline fibres_ ↓alveolar bone resorption, ↓Pocket
probing depth and clinical attachment level
• Pradeep A R et al (2012)( chronic periodontitis)
,Alendronate Local drug delivery as 1% gel_ ↑% of bone
fill , ↓Pocket probing depth , clinical attachment level
• Pradeep A R et al (2012) (aggressive periodontitis)
Alendronate Local drug delivery as 1% gel _↑% of bone
fill, ↓Pocket probing depth , clinical attachment level,

40. As these human studies indicate, local drug delivery
of bis- phosphonates show a ray of hope in the use
of these drugs as local host modulating agents in
periodontal therapy. This mode of application can
overcome the adverse effects associated with
systemic administration of bisphosphonates, while at
the same time retaining the property of bone sparing.

41. BISPHOSPHONATES
AS ANALGESICS

42. PRE- CLINICAL STUDIES
DOSE DEPENDENT ANALGESIC EFFECT in
animal models of inflammatory pain, cancer
pain, neuropathic pain
• Goicoechea et al., J Pharmacol, 1999;
• Cui et al., Pain, 2000;
• Oelzner et al. Inflamm Res, 2000;
• Bonabello et al., Pain, 2001;
• Walker et al., Pain , 2002;
• Harada et al., Inflamm Res, 2004;
• Kawabata et al., Neuropharmacology,
2006;
• Bianchi et al., European Journal of Pain,
2007;

43. IV PAMIDRONATE AS ANALGESIC
• Metastatic bone pain
• Ankylosing spondylitis
• Paget’s disease
• Rheumatoid arthritis
• Chronic back pain
( Hortobagyi et al., 1996; Lipton et al., 1994; Maksymowych et
al., 1998; Van Offel et al., 2001; Maccagno et al., 1994;
Kubalek et al., 2001; Fulfaro et al., 1998; Varenna et al.,
2000; Pappagallo et al,. 2003)

44. CONTRA-INDICATIONS

45. • Sensitivity to phosphate.
• GI upset
• Parathyroid dysfunction
• Pregnant or breast feeding mothers
• Kidney or hepatic trouble

46. • Hypocalcemia
• Poor Oral Hygiene and Active Endodontic /
Periodontal Disease
Nase JB, Suzuki JB (August 2006)

47. DRAW BACKS

48. • Chronic administration over long periods to be
effective.
• High cost and accessibility.
• A full body irradiation that would occur since these
agents have to be administered IV.

49. SIDE-EFFECTS

50. • 1. Gastro intestinal intolerance, e.g., drug induced
oesophagitis.
• 2. Renal toxicity
• 3. Hypocalcaemia caused by reduced bone
resorption leading to reduced calcium efflux from
bone
• 4. Hepatotoxicity
• 5. Acute phase reaction- transient and
manageable
• 6. Ocular inflammation
• 7. Dermatologic reactions
• 8. Osteonecrosis of jaws seen after tooth
extraction because of over suppression of bone
turnover.
• 9. Changes in White blood cell count.
• 10. Atrial fibrillation
(N Engl J Med. 2007;356(18):1809–1822)

51. • Oral bisphosphonates can cause
upset stomach and inflammation and erosions of
the esophagus, which is the main problem of
oral N-containing preparations. This can be
prevented by remaining seated upright for 30 to 60
minutes after taking the medication.
• Intravenous bisphosphonates can give fever
and flu-like symptoms after the first infusion,
which is thought to occur because of their potential
to activate human T cells. These symptoms do not
recur with subsequent infusions.
• FDA Review 2008: don’t factor atrial fibrillation in
bisphosphonate decision

52. OPTIMAL DURATION OF USE FOR
BISPHOSPHONATES
• Bisphosphonates effective in reducing
fractures for up to 4.5 years (trials)
• What is optimal duration of treatment?
– Longer treatment may further decrease
fracture risk
– On the other hand, concerns have been raised
that longer treatment may compromise bone
quality and lead to increased fracture risk
• Long term fracture trials are not feasible so
must rely on extensions of shorter studies

53. OSTEO-RADIO NECROSIS OF JAW

54. BRONJ
• First recognized in 2003 as a complication of
bisphosphonate therapy
• Higher frequency in the mandible (63%) than in the
maxilla (38%)
• Etiology is unclear and is the subject of current
research and investigation

55. BIONJ
• Can be related to dental treatment
• Can be related to dental pathology
• Can be spontaneous with dental etiology
• Can be related to denture irritation or wear
• can be unrelated to any of the above
• Can be related to local trauma
• Can be unknown in etiology

56. in a subgroup of oncological patients
(multiple myeloma, breast, prostate,
lung cancer bone metastases)
receiving prolonged treatment with
potent bisphosphonates (i.e. monthly
IV administration)

57. DIAGNOSIS
• A diagnosis of bisphosphonate-associated
osteonecrosis of the jaw relies on three
criteria:
1. the patient possesses an area of exposed
bone in the jaw persisting for more than 8
weeks,
2. the patient must present with no history
of radiation therapy to the head and neck,
3. the patient must be taking or have taken
bisphosphonate medication.
American Dental Association/National Osteoporosis

58. According to the updated 2009 BRONJ Position
Paper published by the American Association of
Oral and Maxillofacial Surgeons, both
the potency of and the length of exposure to
bisphosphonates are linked to the risk of
developing bisphosphonate-associated
osteonecrosis of the jaw
AAOMS Updates BRONJ Position Paper, January 23, 2009

59. STAGE 1
Characterized by
exposed bone that
is asymptomatic
with no evidence
of significant soft
tissue infection

60. STAGE 2
Exposed bone
associated with pain,
soft tissue and/or bone
infection

61. STAGE 3
Exposed bone
associated with
soft tissue
infection or pain
that is not
manageable with
antibiotics due to
the large volume
of necrotic bone.

62. STAGE 3( CONTD.)
Pathologic
fracture

63. ONJ
• Bone histology - necrosis and osteomyelitis
• Microbiology - actinomycetes and mixed
bacteria

64. A 40 YEAR FEMALE WITH A DIAGNOSIS OF
BREAST CANCER AND ZOMETA THERAPY (6
MONTHS) PRESENTS WITH PAIN, EXPOSED AND
INFECTED MAXILLARY BONE FOLLOWING
EXTRACTION

65. RELATIVE POTENCY
• Etidronate (Didronel) 1
• Tiludronate (Skelide) 10
• Pamidronate (Aredia) 100
• Alendronate (Fosamax) 1,000
• Risedronate (Actonel) 10,000
• Ibandronate (Boniva) 10,000
• Zolendronic acid (Zometa) >100,000

66. ONJ: INCIDENCE ESTIMATES
• Incidence in patients treated for cancer
2.5%-5.4%
Incidence in case of osteoporosis
0.007%- 0.04%
By 2006, safety databases (USFDA, Novartis,
Research on Adverse Drug Events And Reports
project) included 3,061 total cases of ONJ

68. • From April 1999 until May 2006, 10 of 310 (3%)
patients with ONJ while receiving bisphosphonate
therapy
• Except one, all ONJ patients had recent dental
extractions

69. Matrix metalloproteinase 2 (MMP2) is a
candidate gene for bisphosphonate-induced
ONJ for 3 reasons:
1) MMP2 is associated with bone abnormalities
which could be related to ONJ.
2) 2) Bisphosphonates are associated with atrial
fibrillation, and MMP2 is the only gene
known to be associated with both bone
abnormalities and atrial fibrillation.
3) 3) A network of disorders and disease genes
linked by known disorder-gene associations
indicates that cardiovascular disease and
bone disease are closely related, suggesting
that a single drug such as bisphosphonate,
acting on a single gene, MMP2, could have
both bone and cardiovascular side effects
different from the osteoclast inhibition that
is characteristic of bisphosphonate

70. RISK FACTORS
• Poor oral hygiene
• Dental procedures (tooth extractions,
implants)
• Chemotherapy
• Corticosteroid use
• Coagulopathies
• Immunosuppression / post-
transplantation
• Local cancerous invasion

71. • Local radiation therapy
• Heavy nicotine use
• Oral herpes infection
• Episodes of osteonecrosis / osteomyelitis
Others? (white phosphorus?, pyrophosphate
in tooth paste?, statins?)

72. REPORTED FACTORS
LEADING TO BRONJ
• Extractions
• RCT
• Periodontal infections
• Periodontal surgery
• Implant surgery

73. EVALUATION
• C-terminal telopeptide, commonly known as CTX,
a serum biomarker for bone turnover rate and a
tool used to evaluate patient risk for
complications due to BRONJ
• Reduced CTX values, Increase risk

74. PHOSSY JAW : 1830 -
1910
ONJ caused by exposure
to white phosphorus
(WP)
Workers in the match
industry were
exposed to WP fumes
during mixing and
spreading of the dip
material.
Painful toothaches
and over time,
abscesses of the jaw
bone.

75. White Phosphorus
 Elemental phosphorus
can exist in several
allotropes, most
commonly white, red,
and black.
 WP is used for signaling,
smoke-screening,
incendiary (military)
purposes; however
 WP is also the most
abundant form of phosphorus
produced industrially.
 Most forms of phosphorus
chemicals are produced from
WP, including chemicals in
fertilizers, food additives,
pesticides, sodas, tooth-
paste, cleaning compounds,
and drugs (e.g. illicit
production of
methamphetamine)

76. TREATMENT
• Antimicrobial mouth washes and oral antibiotics
to help the immune system fight the attendant
infection,
• Local resection of the necrotic bone lesion.
• Many patients with BRONJ have successful
outcomes after treatment, meaning that the local
osteonecrosis is stopped, the infection is cleared,
and the mucosa heals and once again covers the
bone.

77. • There is no known prevention for bisphosphonate-
associated osteonecrosis of the jaw.
• Avoiding the use of bisphosphonates is not a viable
prevention on a general-population basis because the
drugs have more benefit throughout the population
(preventing osteoporotic fractures and treating bone
cancers) than harm (BRONJ)
American Dental Association/National Osteoporosis
Foundation, 2008

78. Dental Management of Patients
Receiving Oral Bisphosphonate Therapy

79. • The recommendations focus on conservative surgical
procedures, proper sterile technique, appropriate use
of oral disinfectants and the principles of effective
antibiotic therapy.
• Because of a paucity of clinical data on the dental
management of patients on oral bisphosphonate
therapy, these recommendations primarily are based
on expert opinion.
• Intended to help dentists make clinical decisions.

80. GENERAL RECOMMENDATIONS
• Routine dental treatment generally should not
be modified solely due to use of oral
bisphosphonates.
• All patients should receive routine dental
examinations.
• All patients taking the drug should be
informed that:
 Oral bisphosphonate use places them at very
low risk for developing BON.
The low risk for developing BON may be
minimized but not eliminated.

81.  An oral health program consisting of sound oral
hygiene practices and regular dental care may be
the optimal approach for lowering the risk for
developing BON.
There is no validated diagnostic technique
currently available to determine if patients are at
increased risk for developing BON.
Discontinuing bisphosphonate therapy may not
eliminate any risk for developing BON.

82. • The patient also should be informed of the
dental treatment needed, alternative treatments,
how any treatment relates to the risk of BON.
• The patient should be encouraged to consult
with his/her physician about health risks
associated with discontinuation of
bisphosphonate treatment.
• BON can occur spontaneously, due to dental
disease or secondary to dental therapy.
Therefore, patients taking oral bisphosphonates
should be instructed to contact their dentist if
any problem develops in the oral cavity.
• The dentist should retain in his/her file the
acknowledgment and consent for the treatment.

83. MANAGEMENT OF PERIODONTAL
DISEASES
• Bisphosphonate users who have active
periodontal diseases should receive appropriate
forms of non-surgical therapy, which should be
combined with the commonly recommended re-
evaluation at four to six weeks.
If the disease fails to resolve, the goal of surgical
treatment should be to obtain access to root
surfaces.
When necessary, modest bone re-contouring
techniques should be used.

84. At this time, there is no evidence that :
• periodontal procedures such as guided tissue
regeneration or bone replacement grafts increase or
decrease the risk for BON or success of implant treatment.
• Use of such techniques should be judiciously considered
based on patient need.
• Primary soft tissue closure following periodontal surgical
procedures is desirable, when feasible.
• Patients without periodontal disease should receive
preventive therapy for periodontal disease. Patients should
be regularly monitored.

85. IMPLANT PLACEMENT AND
MAINTENANCE
• There is a paucity of data on the effects of implant
placement in patients taking oral bisphosphonates.
• Because implant placement requires the preparation
of the osteotomy site, treatment plans should be
carefully considered.
• The patient may be at increased risk for BON when
extensive implant placement or guided bone
regeneration is necessary to augment the deficient
alveolar ridge prior to implant placement.

86. • Before implant placement, the dentist and the
patient should discuss the risks, benefits and
treatment alternatives.
• Maintenance of implants should follow accepted
mechanical and pharmaceutical methods to
prevent peri-implantitis, with regular monitoring
of the patient.

87. ORAL AND MAXILLOFACIAL
SURGERY
• When treatment of dental and/or periodontal diseases has
failed, surgical intervention may be the best alternative.
• Patients receiving oral bisphosphonates who are undergoing
invasive surgical procedures should be informed of the risk,
although small, of developing BON.
• Alternative treatment plans should be discussed with the
patient, which include:
 endodontics (including endodontic treatment followed by
removal of the clinical crown),
allowing the roots to exfoliate (instead of extraction),
bridges and partial dentures (instead of implant placement).

88. • If extractions or bone surgery are necessary,
conservative surgical technique with primary tissue
closure, when feasible, should be considered.
• In addition, immediately before and after any surgical
procedures involving bone, the patient should gently
rinse with a chlorhexidine until healed.
• The regimen may be extended based on the patient’s
healing progress.
• Prophylactic antibiotics after a surgical procedure
should be based on the risk of an infection and NOT
because the patient is taking a bisphosphonate.
• There is no evidence that the use of antibiotics is
effective in preventing BON.

89. ENDODONTICS
• Endodontic treatment is preferable to surgical
manipulation if a tooth is salvageable.
• Routine endodontic technique should be used.
• Manipulation beyond the apex is not
recommended.
• In some situations, depending on risk,
endodontic treatment of non-restored teeth after
removal of the clinical crown, which allows
passive exfoliation of the root tip, may be
considered.

90. RESTORATIVE DENTISTRY
AND PROSTHODONTICS
• There is no evidence that malocclusion or
masticatory forces increase the risk for BON.
• All routine restorative procedures may be
conducted.
• Prosthodontic appliances in patients should be
promptly adjusted for fit in order to avoid ulceration
and possible bone exposure.

91. UNRESOLVED
QUESTIONS????????

92. • Bisphosphonates have been and continue to be used for
other conditions without an FDA-approved indication for
therapy.
• As noted, these include various pediatric populations
with low bone mass, incident fractures, and prolonged
immobility.
• Many healthy premenopausal women with either
radiographic osteopenia or osteoporosis without
fractures and postmenopausal women with osteopenia
but without fractures now receive bisphosphonate
therapy.
• Until further studies address these important clinical
questions, it is important to tell such patients that we
currently lack sufficient data from well-controlled clinical
trials to determine either benefits or risks assumed with
these pharmacological interventions.

93. The 2014 update of a position paper from the
American Association of Oral and Maxillofacial
Surgeons recommended changing the name of
bisphosphonate-related osteonecrosis of the
jaw (BRONJ) to medication-related
osteonecrosis of the jaw (MRONJ), owing to the
increased number of maxillary and mandibular
osteonecrosis cases that have been linked to
other antiresorptive (denosumab) or
antiangiogenic treatments