Continuing Relief of Pain with Long Term Treatment for Osteoporosis with Intravenous Pamidronate

Purpose: Bisphosphonates are valuable in reducing the incidence of fracture. Side effects limit persistence with oral therapy and long term studies of pain relief are difficult to pursue. Intravenous bisphosphonates offer an alternative treatment to oral bisphosphonates and are tolerated over a longer period. The use of Pamidronate, an intravenously administered bisphosphonate, to benefit pain and reduce fracture incidence in the long term has not been extensively investigated. The study aimed to investigate the effect of Pamidronate on pain, vertebral fracture incidence and Bone Mineral Density over 6 or more years.Methods: Patients were offered intravenous Pamidronate if oral treatment with bisphosphonates or Hormone replacement therapy had failed due to side effects, fractures continued on oral treatment or oesophageal reflux led to cessation of oral treatment. Pain was assessed using the Nottingham health profile; radiographs were used to evaluate vertebral fracture and DXA measured bone mineral density.Results: The primary outcome was the pain domain. Median patient follow up was 9 years. Pain had improved significantly (p = 0.03) and in 68% pain had either improved or remained unchanged. Vertebral fractures occurred in 14% of patients in the first 3 years, 9.5% in years 4-6, but increased in years 7-9 to 27%. Bone mineral density increased in the lumbar spine (p < 0.001) but not at the femoral neck.Conclusions: Pamidronate had a beneficial effect on pain over the period of the study. Vertebral fracture incidence increased after 6 years of Pamidronate, although spine BMD increased significantly.

Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab

Modern medications for osteoporosis (bisphosphonates, denosumab, teriparatide) are well-tolerated drugs, which can significantly lower vertebral and non-vertebral fracture risk according to prospective and observational studies in up to 10-year period. Certain drugs (denosumab, teriparatide) are active only during the treatment period and do not prevent bone loss and fracture risk after discontinuation, while such protective effect is observed in bisphosphonates. Despite impressive success of continuous 10-year denosumab treatament of severe osteoporosis, some of the recently published data suggest that vertebral fracture incidence is increased after treatment discontinuation, along with multiple vertebral fracture incidence, especially in patients with previous fractures. Issues of osteoporosis treatment duration, sequential use of osteoporosis drugs and criteria for treatment discontinuation are now in focus of attention. European Medicines Agency (EMA) and European Calcified Tissue Society (ECTS) considered these issues in 2017. ЕМА considered fractures after denosumab discontinuation as a natural disease course and did not recommend any changes in product instruction. The main conclusion of ECTS is that the possibility of multiple fractures development after denosumab discontinuation exists, however, there is still not enough firm evidence, as well as effective countermeasures. Clinicians and patients should be aware of potential risk. Both EMA and ECTS suggest considering denosumab treatment or discontinuation after 5-year treatment period or possibly replacing with bisphosphonates. Recent data suggest that prolonged osteoporosis treatment can be done in accordance with the concept of treatment until target goal (for example, achievement of femoral T-score -2.0SD and higher). In our review, we focus on recent data concerning the issues stated above. This topic was also discussed on Russian Osteoporosis Association (ROA) expert meeting in Saint Petersburg on 24 may 2018, chaired by ROA president, professor Olga Lesnyak and Columbia University professor, J.P. Bilezikian. As a result, an Expert Council resolution was written and introduced in the article.

Aging of bone

In Europe, vertebral fracture incidence has increased 300–400% for women and more than 400% for men during the last 30 years. These data are age-adjusted and therefore highlight that there is a decrease in bone mass or bone quality from generation to generation. To arrest or reverse the increases in osteoporotic fractures, effective general preventive regimens must be established. However, in order to do so, basic understanding of age-related changes in the material quality, 3D cancellous bone architecture, macrostructure (shape and size), and strength of human bone is crucial.