Risk of developing spontaneous MRONJ in fibrous dysplasia patients treated with bisphosphonates: a systematic review of the literature.

OBJECTIVE: The objective of this systematic review was to evaluate the risks of medication-related osteonecrosis of the jaw (MRONJ) in fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) patients treated with bisphosphonates. METHOD AND MATERIALS: A systematic review of the literature was performed by searching PubMed and Embase databases using MeSH terms (fibrous dysplasia of bone, "fibrous dysplasia, polyostotic," osteonecrosis, jaw, therapeutics, diphosphonates, denosumab, teriparatide, estrogens, hormones, raloxifene hydrochloride, calcitonin, cathepsin K) and non-MeSH terms (antiresorptive therapy, antiresorptives, bisphosphonate, estrogen therapy, hormone therapy, bazedoxifene, cathepsin K inhibitor). Articles were limited to human studies, in English language, in which patients were on antiresorptives for at least 1 year. PRISMA statement guidelines were used to eliminate non-relevant studies. The PICOT question asked was, "Does exposure to bisphosphonates and other antiresorptives cause occurrence of MRONJ in fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients followed up for at least 1 year?" RESULTS: Eight eligible articles were included in the quantitative synthesis after articles were screened using a PRISMA flowchart. There were 12 reported occurrences of MRONJ among a combined total of 312 fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients (3.85%). CONCLUSION: Patients with fibrous dysplasia or fibrous dysplasia/McCune-Albright syndrome have a low incidence of MRONJ and may apparently have low susceptibility to spontaneous development of MRONJ.

Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients.

In hemodialyzed patients aluminum (Al) intoxication may induce osteomalacic lesions which are mainly observed when plasma immunoreactive parathyroid hormone (iPTH) concentrations are low, and osteitis fibrosa absent. In this study, the bone tissue of eight hemodialyzed patients with elevated plasma and bone Al concentrations was examined by histomorphometry, electron microscopy, and x-ray microanalysis. Five patients (group 1) had osteomalacia and minimal osteitis fibrosa, three patients (group 2) had severe osteitis fibrosa. In group 1, Al was concentrated at the mineralizing front, in hexagonal structures measuring 200 to 1,000 A which also contained phosphorus, but not calcium. Hydroxyapatite needles had a normal aspect. Osteoblasts appeared inactive. In group 2, Al was also present at the mineralizing layer of osteoid, but, in these cases, in small clusters next to abnormal calcium deposits. Osteoblasts appeared very active. Their mitochondria contained calcium and phosphorus granules, or amorphous material, measuring 1,500 to 2,000 A, emitting x-rays characteristic for Al and phosphorus. These results suggest that secondary hyperparathyroidism, by stimulating the cellular activity, may increase the uptake and release of Al by the osteoblasts. The presence of Al within the mitochondria of these cells may be one of the factors inducing the mineralization defect.

Bone disease in hemodialysis patients with particular reference to the effect of fluoride.

Forty-one patients on our chronic hemodialysis program were assessed for the degree of progression of bone disease over an average period of 46 months. Seven patients were using a fluoridated dialysate. Four of these seven patients developed a marked increase in osteoid as judged by bone biopsy, while in the nonfluoridated group the amount of osteoid remained within normal limits.In the absence of fluoride, although osteitis fibrosa occurred, it was reversible in 10 out of 12 cases by dihydrotachysterol treatment, and overall there was no evidence of progression of bone disease at the end of the study period.