Strontium—the element that strengthens bones, but nobody talks about it?

Aim of the study: Strontium ranelate is a new treatment for osteoporosis, so its benefits and harms need to be known. To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis.

Results: Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo, and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment, nor did they increase the risk of serious side effects, gastritis or death.

Aim of the study: Significant progress has been achieved in osteoporosis treatment, in terms of agents with novel mechanisms of action, of new schedules of administration, and of long-term treatment safety demonstration. Alendronate, ibandronate, intranasal calcitonin, parathyroid hormones, raloxifene, risedronate, hormone replacement therapy, strontium ranelate and zoledronate decrease the risk of vertebral fracture.

Results: Strontium ranelate is a new agent for the treatment of osteoporosis, with antifracture efficacy whatever the severity of osteoporosis. An extension of the phase 3 trials up to 5 years has shown sustained antifracture efficacy. The humanized monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL), denosumab, causes a rapid, high-magnitude, dose-dependent inhibition of bone resorption. Spine, hip and forearm bone mineral density increased, to an extent slightly higher than with the weekly administration of 70 mg alendronate.

Aim of the study: Glucocorticoid-induced osteoporosis (GIOP) has emerged as a challenge after long-term glucocorticoid administration during the clinical therapy of diverse diseases. Although some candidates for GIOP treatment have been explored, there is still a lack of reliable drugs for GIOP prevention.

Results: GluSr also effectively promoted osteoblast survival, inhibited osteoclast differentiation and restored bone formation in GIOP rat models. Microarray analysis of the femora from GIOP rats treated with GluSr revealed that the signalling pathways of the glucocorticoid receptor (GR), oestrogen receptor gene (ESR) and vitamin D receptor (VDR) were involved in bone restoration by GluSr. In summary, our study proved that GluSr enhanced osteoblast differentiation and suppressed osteoclast activity both in vitro and in vivo. GluSr might function as a novel strontium reagent for GIOP prevention.

Aim of the study: Osteoporosis in men contributes to significant morbidity and mortality, yet is underrecognised. Hip fractures in men are associated with greater mortality (up to 37.5% in the first year) compared with women. Timely diagnosis and treatment of osteoporosis in men are therefore critical. Secondary causes for osteoporosis are common and need to be excluded. Absolute fracture risk assessment guides selection of men for anti-osteoporotic therapy.

Results: Most studies of oral or intravenous (i.v.) bisphosphonate therapy in hypogonadal and eugonadal men with osteoporosis have reported effects on bone mineral density (BMD) and biochemical bone turnover markers, rather than fragility fractures. Intravenous zoledronic acid given to elderly men and women after hip fracture reduced clinical, clinical vertebral and nonvertebral fractures, and mortality compared with placebo infusions. Recent studies in men with osteoporosis have reported reductions in vertebral fractures with oral or i.v. bisphosphonates. All studies have been underpowered to detect reductions in nonvertebral and hip fractures. Teriparatide treatment also reduces vertebral fractures. Denosumab increases BMD and reduces bone turnover markers, while strontium ranelate increases BMD in men with osteoporosis.

Aim of the study: Calcium, magnesium and strontium have all been implicated in both musculoskeletal and cardiovascular health and disease. However, despite these three elements being closely chemically related, there is marked heterogeneity of their characteristics in relation to cardiovascular outcomes.

Results: There is little evidence to support routine magnesium supplementation for musculoskeletal outcomes; greater dietary intake and serum concentrations appear protective against cardiovascular events. Strontium ranelate, which is now available again as a generic medication, has clear anti-fracture efficacy but is associated with an increased risk of thromboembolic disease. Whilst a signal for increased risk of myocardial infarction has been detected in some studies, this is not supported by wider analyses. Strontium ranelate, under its current licence, thus provides a useful therapeutic option for severe osteoporosis in those who do not have cardiovascular risk factors.

Aim of the study: This study investigated the regulatory effects of strontium-substituted hydroxyapatite (SrHAp) on bone cell regulation, with a specific focus on osteoblast and osteoclast activities. X-ray diffraction verified the successful incorporation of strontium into the hydroxyapatite lattice, confirming the high phase stability despite the presence of a minor amount of CaO.

Results: The morphological analysis of RANKL-treated RAW 264.7 cells revealed a reduction in TRAP-positive multinucleated cells, and this result was supported by decreased TRAP activity. Mechanistic investigations revealed that SrHAp interfered with the RANKL/TRAF6/NF-κB signaling pathway, leading to the downregulation of the master transcription factor NFATc1. In conclusion, SrHAp nanoparticles exhibit dual functions, as they promote osteoblastic mineralization while concurrently arresting osteoclast differentiation. This balanced regulation highlights the potential of SrHAp as a bioactive ceramic for the treatment of osteoporosis and for advanced bone regeneration.

Aim of the study: To optimize osteoporosis therapy with the parathyroid hormone fragment teriparatide (PTH1-34), we sought to determine whether strontium (Sr) could potentiate the bone anabolic action of intermittent PTH1-34 in ovariectomized rats. Female rats were either Sham-operated or ovariectomized (Ovx) at 6 months of age.

Results: PTH1-34 alone), maintained the Sr-induced increase in tissue-level vBMD, and significantly improved bone strength. In primary osteoblast cultures, Sr and PTH1-34, administered either alone or in combination, increased Rankl and decreased Opg expression, consistent with the elevated urinary levels of the bone resorption marker deoxypyridinoline in vivo. Sr or PTH1-34 alone stimulated Igf1 and Alpl expression, whereas co-stimulation further enhanced these osteogenic markers. In conclusion, combining Sr with PTH1-34 integrates the osteoanabolic effects of PTH1-34 on bone mass with the mineral-level effects of Sr on bone material properties, leading to synergistic stimulation of bone formation and superior improvements in bone quality and strength.

Aim of the study: Osteoporosis is a global degenerative bone disorder in the elderly caused by the aging of bone and immune systems. Current therapeutics for osteoporosis focus on medical control over the osteoblast and osteoclast, resulting in complicated procedures and side effects.

Results: In the present work, we have designed a strontium phosphate (SP)-coated hollow zeolitic imidazolate framework-8 (hZIF) nanomedicine by chemical mineralization in which vitamin D3 (VD) has been further encapsulated. The formulated VD@SP-hZIF nanoparticles exhibit robust osteoimmune-regulative effects (anti-inflammatory, pro-osteogenesis, and calcium absorption promotion) in aged murine osteoporotic models respectively due to the constructed moieties of zinc ions, strontium phosphates and the loaded VD. The in-depth osteoporotic therapeutic mechanism of VD@SP-hZIF nanoparticles has also been explored. The present work highlights the construction of the metal-organic framework nanomedicines for effective regulation of osteoimmune microenvironment against osteoporosis, providing a highly applicable therapeutic paradigm towards pathologies with inflammatory disorders.