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Objectives: To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO)., Methods: A prospective, observational study was conducted from 2011 to 2014. Patients with risk factors for complications of percutaneous or surgical ablation or recurrence after ablation, were offered once monthly intravenous bisphosphonate treatment until significant pain alleviation was achieved., Results: We included 23 patients. The first two patients received pamidronate and the next 21 zoledronic acid (mean, 2.95 infusions per patient). Bisphosphonate therapy was successful in 19 patients (83%), whose mean pain visual analogue scale score decreased by 76.7%; this pain-relieving effect persisted in 17 patients (74%) with a mean follow-up time of 36 months. Computed tomography (CT) demonstrated a mean nidus density increase of 177.7% (p = 0.001). By magnetic resonance imaging (MRI), mean decreases were 38.4% for BMO surface area and 30.3% for signal intensity (p = 0.001 and p = 0.000, respectively)., Conclusions: In 17/23 patients with painful OO managed conservatively with bisphosphonates, long-term final success was achieved. Bisphosphonates may accelerate the spontaneous healing of OO., Key Points: • 19/23 patients with OO managed with bisphosphonates experienced significant pain relief • Pain relief was sustained in 17/23 patients, mean follow-up of 36 months • CT demonstrated a significant increase in nidus mineralisation • MRI demonstrated a significant decrease in bone marrow oedema • Bisphosphonate therapy may accelerate the spontaneous healing of OO.

Corticosteroid-induced osteoporosis is common but too often unrecognized, and its management remains insufficient. Bone loss is variable from one patient to another and thus difficult to predict, but all treated patients must be considered at risk. There are tools to assess absolute fracture risk in this case as there are for menopause-associated osteoporosis, and they may help guide the clinician in decision-making. Recent guidelines help the physician to define indications for bone mineral density testing and for therapeutic management. Bisphosphonates are currently the first-line treatment for patients with fractures or elevated fracture risk during corticosteroid treatment.

Bisphosphonates, potent anti-osteoclastic agents, are nowadays the first-line therapy for Paget's disease of bone. Solid evidence about efficacy and the risk/benefit ratio favor tiludronate and risedronate for oral administration and pamidronate for intravenous administration. Treatment is always intermittent, with the frequency of therapeutic sequences depending on the specific drug and the quality and duration of response. Treatment response is assessed by the extent of the reduction of biochemical markers of bone turnover, especially plasma total alkaline phosphatase. The goal of the treatment is to induce full remission, that is, normal levels of alkaline phosphatase. Bisphosphonates should be used in all patients with bone involvement that might create long-term articular (arthropathy) or neurologic (compression) complications. This aggressive strategy is the most likely to provide effective prevention of complications in the long term.

Antiresorptive agents are effective in preventing and treating postmenopausal osteoporosis, provided they are taken as directed. Regular physical examinations including height measurements may fail to ensure optimal compliance. Bone mineral density (BMD) measurement is indispensable for determining whether treatment is warranted. The measurement can be repeated after 2 years at least, provided quality-control procedures are adequate. BMD changes over time should be compared to the least significant change calculated from the in vivo BMD reproducibility at the measurement center. However, BMD changes are not correlated with the fracture risk reduction induced by antiresorptive treatment. Biochemical markers for bone turnover can be monitored after only 3-6 months provided steps are taken to control for intraindividual variability. They are useful when patient compliance is poor or the treatment response inadequate.

The range of bone diseases in which bisphosphonates are used has extended far beyond osteoporosis during the last few years. Bisphosphonate therapy is now so well validated as to be the reference standard in Paget's disease and in the prevention of bone complications related to malignant osteolysis. Promising preliminary findings warrant the use of bisphosphonates in conditions that are either rare (fibrous dysplasia) or severe (pediatric osteogenesis imperfecta). The third category of indications encompasses many conditions in which the limited available data do not warrant widespread use: examples include reflex sympathetic dystrophy syndrome, acute back pain after a vertebral crush fracture, and chronic inflammatory joint disease not treated by glucocorticoids.

OSTEOLYSIS AND HYPERCALCEMIA: Multiple myeloma is a type B high-grade lymphoproliferative syndrome with bone tropism. Bone-related manifestations--osteolysis and hypercalcemia--are observed in 80 and 30% of cases respectively. Excessive bone resorption subsequent to destruction of the bone matrix by osteoclasts is associated with insufficient bone formation. This process plays a determining role in the development of osteolysis and hypercalcemia in multiple myeloma patients. MECHANISM OF BONE DESTRUCTION: The reality and intensity of bone destruction is clearly demonstrated by histomorphometric studies and more recently by biochemical methods using markers of bone resorption. The excessive bone resorption results from complex interactions between tumor plasma cells, bone cells, and stem cells and involves local factors and adhesion molecules. BISPHOSPHONATES: Bisphosphonates are powerful inhibitors of bone resorption. They constitute a substantial advance in the management of bone manifestation in patients with multiple myeloma. Bisphosphonates not only have a well-established curative effect in patients with tumor-induced hypercalcemia, but also inhibit disease progression in bone.