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Introduction: Paget's disease of bone (PDB) is a focal bone disorder caused by a marked dysregulation of osteoblasts and osteoclasts in basic multicellular units, leading to abnormal and disorganized deposition of collagen fibers (the so-called 'woven bone'). Therefore, pagetic bones are increased in size, and at increased risk for bone pain, deformities, fractures, osteoarthritis, and, more rarely, neoplastic degeneration., Areas Covered: In this review, we revise the available information concerning the pharmacological treatment of PDB., Expert Opinion: PDB progresses slowly within the affected skeletal sites and, if untreated, often leads to bone overgrowth, with bone pain, deformity, and a likely increased risk of complications. Thus, the primary goal of treatment is the restoration of a normal bone turnover, in order to relieve bone pain or other symptoms and possibly prevent the complications. PDB long remained a poorly treatable disorder until the discovery of antiresorptive agents such as calcitonin first and bisphosphonates (BPs) later. With the recent development of potent intravenous BPs like zoledronate, allowing a better control of disease activity over the long term with a single infusion, has contributed to a marked improvement of the clinical management of this invalidating disorder.

Introduction: Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation., Areas Covered: In this review, the authors summarize the pathophysiology of GIOP and give discussion to the clinical management of patients taking GCs, focusing on the currently available drugs that have antiresorptive or anabolic activity on bone., Expert Opinion: Despite the widespread use of GCs and their well-established detrimental skeletal effects, GIOP remains an under-diagnosed and under-treated condition. Indeed, the clinical management of GIOP is still debated, so that the recent guidelines differ in their indications for pharmacological intervention. Either bone mineral density (BMD) or algorithms such as FRAX do not completely account for the remarkable and rapid increase in fracture risk of most GC-treated patients. Moreover, while oral bisphosphonates remain the most used and cost-effective option, the potential increased benefits of more potent antiresorptive agents (e.g. denosumab and zoledronate) or anabolic compounds (e.g. teriparatide) warrant further investigation. Despite the above limitations, the assessment of fracture risk is recommended for all individuals committed to receiving oral GCs for 3 months or longer.

Introduction : Osteoporosis is a chronic, skeletal disorder characterized by compromised bone strength and increased fracture risk; it affects 50% of women and 20% of men. In the past two decades, there have been substantial improvements in the pharmacotherapy of osteoporosis which have yielded potent inhibitors of bone resorption or stimulators of bone formation. Areas covered : This review discusses newly identified targets and pathways and conceptual approaches to the prevention of multiple age-related disorders. Furthermore, it summarizes existing therapeutic strategies for osteoporosis. Expert opinion : Our enhanced understanding of bone biology and the reciprocal interactions between bone and other tissues have allowed the identification of new targets that may facilitate the development of novel drugs. These drugs will hopefully achieve the uncoupling of bone formation from resorption and possibly exert a dual anabolic and antiresorptive effect on bone. Alas, limitations regarding adherence, efficacy on nonvertebral fracture prevention and the long-term adverse events still exist for currently available therapeutics. Moreover, the efficacy of most agents is limited by the tight coupling of osteoblasts and osteoclasts; hence the reduction of bone resorption invariably reduces bone formation, and vice versa. This field is very much 'a work in progress.'

Introduction: Osteoporosis is a skeletal disorder characterized by loss of bone mass and strength affecting up to 30-50% of postmenopausal women worldwide. Current therapeutic options include antiresorptives such as aminobisphosphonates or denosumab and osteoanabolic compounds such as teriparatide. Areas covered: In this review, the authors summarize the clinical development, safety and efficacy profile of abaloparatide, a new osteoanabolic agent recently marketed in the US for the treatment of postmenopausal osteoporosis in women who are at high risk for fracture or who fail antiresorptive therapy. Expert opinion: Abaloparatide is a 1-34 PTH related peptide-like molecule that has been modified in order to potentiate the osteoanabolic effect. In its pivotal phase 3 trial in postmenopausal women with osteoporosis, subcutaneous abaloparatide 80 mcg/day reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo and reduced the risk of major osteoporotic fractures compared with teriparatide. These results, together with a reduced prevalence of hypercalcemia and a lower cost of the marketed compound, point toward improved cost effectiveness with abaloparatide versus teriparatide. However, some concerns have been raised due to a somewhat higher occurrence of adverse effects (particularly with palpitations and increased heart rate) or the resultant discontinuation due to these adverse effects when compared to teriparatide.

Introduction: Osteoporosis is a chronic, skeletal disorder characterized by compromised bone strength and increased risk of fractures, affecting up to 50% of postmenopausal women worldwide. Over the past 2 decades there have been consistent developments in the pharmacotherapy of osteoporosis with the availability of potent inhibitors of bone resorption (bisphosphonates, and denosumab) or stimulators of bone formation (PTH analogs) with substantial improvements over calcitonin or estrogen replacement., Areas Covered: In this review we summarize the effects of existing treatment options for postmenopausal osteoporosis along with the unmet clinical needs and we discuss about the potential benefits of new compounds under development., Expert Opinion: Despite the recent progresses, there are still limitations and unmeet needs with all the available drugs, mainly concerning treatment adherence, efficacy on the prevention of nonvertebral fractures and the long-term adverse events of antiresorptive regimens. Moreover, PTH analogs are the only available compounds able to stimulate bone formation, but with a restricted anabolic window of no more than 2 years. Of interest, the more recent advances in bone biology identified new targets for the development of drugs with a more potent and selective activity on either osteoclasts or osteoblasts, thus making possible to uncouple bone formation from bone resorption.

Introduction: Toremifene is a triphenylethylene selective estrogen receptor modulator (SERM) that differs from tamoxifen in a single chloride ion addition on a side chain, resulting in a potentially more favorable toxicity profile., Areas Covered: This article reviews the pharmacokinetics of toremifene and its potential use for the treatment of osteoporosis. This article was based on articles found through a literature search containing the terms 'toremifene' and 'SERMs.', Expert Opinion: Toremifene can be administered orally with an excellent bioavailability. The overall pharmacokinetic profile is remarkably similar to tamoxifen. Toremifene is highly metabolized in the liver and is eliminated primarily in the feces following enterohepatic circulation. Some of its metabolites retain biological activity. This SERM was approved by the FDA for the treatment of estrogen receptor-positive metastatic breast cancer and is under investigation for its potential skeletal benefits in men on androgen deprivation therapy. Despite the positive preclinical and clinical evidences for the prevention of bone loss and fractures, the chemopreventive effect on prostate cancer remains to be confirmed and an increased risk of venous thromboembolism was evidenced in a large Phase III trial. Thus, additional data are required to establish the full clinical profile of this compound and its potential advantages over antiresorptive agents commonly in use for the treatment of osteoporosis.

Osteoporosis is a common skeletal disorder with a strong genetic component. In recent years, significant progress has been made in understanding the genetic basis of osteoporosis. Given the biological significance of signalling through steroid hormone receptors, bone biology and calcium homeostasis, alleles of steroid hormone receptor genes have been postulated to contribute to the well-documented genetic predisposition to osteoporosis; and in different studies, these alleles have been associated with variation in bone mass and fracture risk. Even though results are still conflicting and the molecular mechanisms by which these polymorphisms influence receptor activity remain, in part, to be investigated, an additional important issue is represented by potential pharmacogenomic (the investigation of variations of DNA or RNA characteristics as related to drug response) or pharmacogenetic (the influence of variations of DNA sequence on drug response) implications. In fact, steroid hormone receptors actually mediate the action of several compounds known to positively or negatively affect bone homeostasis, such as vitamin D, estrogen and glucocorticoids. This review analyses major pharmacogenetic studies of polymorphisms in steroid hormone receptor genes.