Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/therapeutic use* ; Humans ; Reproducibility of Results ; Rodentia

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.
Angiogenesis Inhibitors ; therapeutic use ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; drug therapy ; Bone Density Conservation Agents ; adverse effects ; Denosumab ; therapeutic use ; Diphosphonates ; Humans

OBJECTIVE: To determine the effect of alendronate on glucocorticoid-induced osteoporosis(GIO). METHODS: Thirty-five GIO patients were enrolled. Ten milligrams alendronate were prescribed daily for 6 months. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometer (DEXA) after and before the treatment. RESULTS: BMD at lumbar, neck and trochanter sites of the 35 patients after the treatment was significantly increased compared with those before the treatment (P<0.05). Urine Ca/Cr level was decreased (P<0.05). There was no severe side effect. CONCLUSION Alendronate is effective and well tolerated for GIO.
Adult ; Alendronate ; therapeutic use ; Bone Density ; drug effects ; Bone Density Conservation Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; chemically induced ; drug therapy ; Prednisone ; adverse effects ; therapeutic use ; Rheumatic Fever ; drug therapy

OBJECTIVETo investigate the effect and safety of zoledronic acid (Zoledex) in patients with cancer-induced hypercalcemia.

METHODSSeventeen patients with cancer-induced hypercalcemia (corrected blood calcium > 2.70 mmol/L) were treated intravenously by 4 mg zoledex within 15 minutes on the first day. The corrected blood calcium was observed every 4 days in the following 28 days.

RESULTSThe response rate was 94.1% (16/17). The mean corrected blood calcium became normal after the first dose of zoledex (P < 0.01). The lowest value was found on the fourteenth day after treatment. The main side effects consisted of fever (29.4%, 5/17), hypocalcemic tetany (11.8%, 2/17) and arythmia (5.9%, 1/17).

CONCLUSIONZoledex is effective and safe in the treatment of patient with cancer-induced hypercalcemia.

Adult ; Aged ; Aged, 80 and over ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Diphosphonates ; adverse effects ; therapeutic use ; Female ; Humans ; Hypercalcemia ; drug therapy ; etiology ; Imidazoles ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Neoplasms ; complications ; Safety

To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteoporosis. The changes were compared in bone mineral density (BMD), bone metabolism markers and adverse events after 12 months oral administration of risedronate sodium. BMD was measured by dual energy X-ray absorptionmetry (DEXA) and bone turnover marker was detected. The results showed that there was a significant increase in BMD of the lumbar spine (3.29% +/- 1.18%, 4.51% +/- 1.64% respectively) after 6 and 12 months in the risedronate treatment group versus placebo control group (-0.62% +/- 0.24%, 0.48% +/- 0.18% respectively). Bone turnover was decreased to a stable nadir over 6 and 12 months for resorption markers [N-Telopeptide (NTx), P < 0.05] and over 12 months for formation marker (ALP, P < 0.05; BGP, P < 0.05). The safety profile of risedronate sodium was similar to that of placebo. There were no trends toward increased frequency of any adverse experience except for gastrointestinal symptoms (7.1%), rash (7.1%) and hematuria (3.6%), which were usually mild, transient, and resolved with continued treatment. It was concluded that risedronate was an efficacious and safe drug in treatment of postmenopausal osteoporosis.
Alkaline Phosphatase/blood ; Alkaline Phosphatase/drug effects ; Bone Density ; Bone Density Conservation Agents/adverse effects ; Bone Density Conservation Agents/*therapeutic use ; Double-Blind Method ; Etidronic Acid/adverse effects ; Etidronic Acid/*analogs & derivatives ; Etidronic Acid/therapeutic use ; Osteoporosis, Postmenopausal/*drug therapy ; Safety

No abstract available.
Arthritis, Rheumatoid/*drug therapy ; Bone Density Conservation Agents/*therapeutic use ; *Decision Support Techniques ; Female ; Glucocorticoids/*adverse effects ; Humans ; Osteoporosis/*chemically induced/*prevention & control

Aromatase Inhibitors ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone Density Conservation Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; Calcium ; therapeutic use ; Diphosphonates ; therapeutic use ; Female ; Fractures, Bone ; chemically induced ; prevention & control ; Humans ; Imidazoles ; therapeutic use ; Osteoporosis, Postmenopausal ; chemically induced ; diagnosis ; prevention & control ; Postmenopause ; Vitamin D ; therapeutic use

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.
Spinal Fractures/prevention & control/radiography ; Osteoporosis, Postmenopausal/*drug therapy ; Middle Aged ; Lumbar Vertebrae/*drug effects ; Humans ; Female ; Etidronic Acid/adverse effects/*therapeutic use ; Bone Density Conservation Agents/adverse effects/*therapeutic use ; Bone Density/*drug effects ; Biological Markers/blood/urine ; Back Pain/drug therapy ; Alendronate/adverse effects/*therapeutic use ; Aged, 80 and over ; Aged

PURPOSE: The short-term safety and efficacy of zoledronic acid for the treatment of skeletal metastasis was evaluated in patients with hormone-refractory prostate cancer. PATIENTS AND METHODS: A total of 19 hormone-refractory prostate cancer patients with bone metastases were enrolled. All patients received up to six infusions of zoledronic acid (4mg, given intravenously over 15 minutes, every 3-4 weeks). Safety was assessed by monitoring a`dverse events and serum creatinine levels. Efficacy was assessed by monitoring skeletal-related events, brief pain inventory score, quality of life score, type of pain medication, and analgesic score. Mean age of patients was 67.3 years (46-86 years), mean time from diagnosis of bone metastases was 27.6 months (0-117 months), and mean time from diagnosis of hormone-refractory disease was 7.5 months (0-26 months). RESULTS: There was no clinically significant change in serum creatinine levels. Eleven adverse events (musculoskeletal disorders and systemic disorders) in 8 patients were classed as having a possible relationship to study drug. Fifteen patients completed six courses of zoledronic acid infusion. There were no significant changes in the brief pain inventory composite scores, quality of life questionnaire scores or analgesic score. No new skeletal-related events developed during the treatment period. CONCLUSION: Zoledronic acid administered in this study as a 15-minute infusion demonstrated an acceptable and well-known safety profile in patients with refractory prostate cancer with bone metastases. However, prospective placebo- controlled clinical trials are required to elucidate the efficacy of zoledronic acid.
Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Bone Density Conservation Agents/adverse effects/therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Creatinine/blood ; Diphosphonates/adverse effects/*therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Imidazoles/adverse effects/*therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Prostatic Neoplasms/*drug therapy/pathology ; Quality of Life ; Treatment Outcome

Osteoporosis is a major, growing healthcare issue. This is especially of concern in an ageing population like that of Singapore. Osteoporotic patients are at risk of fractures, which can result in increased morbidity and mortality. The use of antiresorptive therapy with bisphosphonates or denosumab has been proven to reduce fracture risk. However, the use of these medications has rarely been associated with the development of osteonecrosis of the jaw, a potentially debilitating condition affecting one or both jaws. Appropriate understanding of the patient's antiresorptive therapy regime, as well as early institution of preventive dental measures, can play an important role in preventing medication-related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral to specialist care is warranted for patients with established MRONJ.
Aged ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Denosumab ; adverse effects ; therapeutic use ; Diphosphonates ; adverse effects ; therapeutic use ; Humans ; Jaw Diseases ; chemically induced ; prevention & control ; Osteonecrosis ; chemically induced ; prevention & control ; Osteoporosis ; complications ; drug therapy ; Osteoporotic Fractures ; complications ; drug therapy ; Risk Factors ; Singapore ; Treatment Outcome