A case of mandible Paget's disease of the bone treated with intravenous neridronate

Paget's disease of bone (PDB) is a focal disorder of osteoclasts, leading to chaotic bone remodelling, and it is characterized by the presence of focal areas of excessive bone formation alongside with areas of focal bone resorption. The typical radiographic feature is the cotton wool appearance. To date, bisphosphonates are the mainstay of the treatment. We hereby report the case of a young woman presenting with mandible PDB, with a relevant diagnostic delay and mistakenly treated for five years with chronic oral corticosteroids. After our evaluation, the patient received treatment with intravenous neridronate (an amino-bisphosphonate licensed in Italy for the treatment of this disease), with achievement of clinical remission

Insight into the WNT system and its drug related response.

The WNT signalling pathway is a complex system for transferring information for DNA expression from the cell surface receptors to cytoplasm and then to the nucleus. It is based on several proteins that work together as agonists and antagonists in order to maintain homeostasys and to promote anabolic processes. The WNT system acts on all cellular lines involved in bone resorption and formation. WNT pathway can mainly be triggered by two different signalling cascades. The first is well known and is the so-called WNT-beta catenin system (or the canonical pathway), the second is known as the non canonical WNT pathway. WNT proteins form a superfamily of secreted glycoproteins. The association with surface receptors, called Frizzled, that are members of the G protein-coupled receptors superfamily and co receptors like low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) complete the WNT system. LRP5/6 show high affinity for WNT antagonists that modulate the activity of this pathway: DKK1 and sclerostin (SCL), that play a crucial role in modulating the WNT system. The WNT-pathway and in particular its antagonists SCL and DKK1 seems to play a key role in the regulation of bone remodeling during treatment with bone active agents such as bisphosphonates, but not only. Their effects become relevant especially in the course of long-term treatments

Radiological features of knee joint synovial chondromatosis

Synovial chondromatosis (SC) is a rare condition with a very variable clinical presentation, thus making the diagnosis not immediate. We report a case of massive primary SC of the knee, properly evaluated with X-rays, ultrasonography and magnetic resonance imaging and successfully treated with an arthroscopic approach

Vitamin D and rheumatic diseases.

Vitamin D has some well-known effects on calcium, phosphate and bone metabolism, but it has recently shown to have many other effects, which may potentially be relevant to patients with extra-skeletal rheumatic diseases. Such effects may be justified by: 1) the presence of the vitamin D receptors also on extra-osseous cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of vitamin D in the control of the transcription of genes involved in rheumatic diseases; 3) the evidence that vitamin D has multiple endocrine effects not only on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys, but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial cells with additional intracrine and paracrine effects. Vitamin D deficiency has been reported in numerous metabolic, degenerative, inflammatory and autoimmune rheumatic diseases. In some cases this association was also related to the risk of developing a rheumatic disease or the degree of disease activity. However there is no conclusive evidence of the efficacy of a preventive or therapeutic strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases. This review aims to provide an overview of the latest evidence concerning the relationship between vitamin D and the most relevant rheumatic diseases

Different fracture risk profile in patients treated with anti-osteoporotic drugs in real-life

In this retrospective study, we intended to investigate the baseline fracture risk profile in patients who started treatment with different anti-osteoporotic medications. We analyzed retrospectively the fracture risk calculated with DeFRA, a validated FRAX derived tool, in women who started an anti-osteoporotic treatment from 2010 to 2017. We analyzed baseline data of 12,024 post-menopausal women aged over 50 years. Teriparatide initiators had a baseline 10-year risk of major osteoporotic fracture of 82.1% with a Standard Deviation (SD) of 66.5%. Denosumab initiators and zoledronic acid initiators had a greater 10-year baseline risk of fracture (54.3%, SD 46.5% and 47.0%, SD 42.0 respectively) than patients initiated on alendronate (24.9%, SD 34.6%) and patients initiated on risedronate (23.9%, SD 24.1%). Using DeFRA, a FRAX™ derived tool, we showed significantly different fracture risk profiles in women who were started on various therapeutic agents for the treatment of osteoporosis in routine clinical practice

how much does an antiinflammatory treatment cost

NSAIDs are among the most popular drugs in the world for their efficacy in controlling pain and acute and chronic inflammation. The efficacy of these therapies is hampered by their safety profile, in particular regarding the gastroenteric tract. The NSAIDs' side effects may heavily influence the health of the single patient and the economy of the health systems. The pharmacoeconomic evaluation of antinflammatory treatment usually considers, in addition to the drug purchase prize, also the shadow costs. This cost is mainly due to the management and prevention of gastropathy. Coxibs, even if more expensive, may become cost-effective for their better gastronteric safety. As a matter of fact, coxib treatment can be considered equivalent to a treatment with NSAID plus PPI. However, the first requirement of these drugs, that should control pain, must be the efficacy and not only safety. In this case the NNT (Number Needed to Treat) is a good marker of efficacy. To calculate the real cost we must pay to reach the target (pain resolution in one patient), we can multiply NNT for the prize of a specific drug. The total cost will depend on drug prize (the cheaper, the better) and on the efficacy expressed by NNT (the lower, the better). In a recent meta-analysis, the NNT of several antinflammatory drugs has been calculated. When the treatment cost was adjusted for its efficacy (NNT), the difference in favour of NSAIDs became so little to disappear because of the higher safety of coxibs (especially of etoricoxiband the possibility to reach antinflammatory and analgesic doses that are difficult to obtain with NSAIDs. Moreover, if also the cost of gastroprotection is considered, the economic impact of NSAIDs can be much higher. In conclusion the pharmacoeconomic analysis of an antinflammatory therapy cannot be based only on safety issues but also on efficacy evaluation that is the main effect we ask to these drugs

Why golimumab in the treatment of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis?

Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis

Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study

Long-term environmental air pollution exposure was associated with osteoporosis' risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure's effect

Vitamin D and fractures: a sistematic review

Vitamin D deficiency is a relevant problem particularly in south Europe and in over 65 year old subjects, that is often underestimated. Vitamin D deficiency represents a real medical emergency also for its role in the patho-physiology of muscular-skeletal diseases. Chronic vitamin D deficiency leads to severe bone and muscular outcomes including: osteoporosis, osteomalacia and proximal limb myopathy. These increase the risk of falling and fractures. The efficacy of vitamin D treatment in decreasing the fracture risk has been reporting in several studies. The negative results of some recent studies questioned the clinical vitamin D efficacy. However these studies have a number of methodological problems and even the interpretation of the results is questionable. In this paper we review all these aspects. This analysis permits to confirm that vitamin D treatment can be extremely cost-effective when given to people at high risk of deficiency. An acceptable compliance is obviously of critical importance