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Jeremy C Thompson,1 Nathan Wanderman,1 Paul A Anderson,2 Brett A Freedman1 1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 2Department of Orthopaedic Surgery, Department of Orthopedics Surgery & Rehabilitation, University of Wisconsin, Madison, WI 53705-2281, USACorrespondence: Brett A FreedmanMayo Clinic, 200 First Street S.W., Rochester, MN 55905, USATel +507 284-2884Fax +507 266-4234Email Freedman.Brett@mayo.eduAbstract: Osteoporosis is a common and debilitating condition characterized by diminished bone mass and architecture leading to bone fragility. Antiresorptive medicines like bisphosphonates (and less commonly denosumab) are the typical first-line agents for the medical treatment of osteoporosis. However, newer anabolic agents have been shown to improve bone mass and architecture, as well as reduce fracture risk, to a greater degree than traditional antiresorptive therapies. Teriparatide (human recombinant parathyroid hormone (PTH) 1– 34, Forteo, Ely Lilly, Indianapolis, IN), which was the first in class to be approved in the United States, is the most widely used anabolic osteoporosis medicine and has shown significant benefit over traditional antiresorptive therapies. However, abaloparatide (synthetic parathyroid-related peptide (PTHrP), Tymlos, Radius Health, Waltham, MA), the second drug in this family, has recently become available for use. In this narrative review, we review the mechanism, effects, and benefits of abaloparatide compared to alternative treatments as well as discuss the current literature in regard to its effect on osteoporosis-related complications in the spine.Keywords: abaloparatide, Tymlos, anabolic, osteoporosis, spine, teriparatide

Recent NMR studies by Nakayama et al. on sodium zeolite A saturated with potassium metal have implied the presence of the anionic Na- species. This, if confirmed, would represent the first observation in a zeolite and opens up a wide range of possibilities for mixed metal zeolitic systems. We report the results of a number of metal combinations, using both sodium and potassium forms of zeolite A as hosts, studied by ESR, solid state MAS-NMR and powder neutron diffraction.

1,2-Dimethylhydrazine-HCl (DMH-2HCl) is derived from the natural toxin cycasin, and is extensively used to induce cancers in experiments with rodents. We examined the toxicity of DMH-2HCl, incorporated into purified diets varying in protein, to determine concentrations compatible with long-term survival in B6C3H1 mice. Initial studies showed single-dose oral LD50 values (95% confidence intervals) of 26 (18-32) mg DMH-2HCl/kg body weight for males, and 60 (53-65) for females. A 6-wk study was performed with diets containing 10 or 40% soybean protein with doses of 0, 11.25, 22.5, 45, 90, and 180 mg DMH-2HCl/kg diet. All mice fed the highest dose were removed from the study due to severe toxicity. Declines in food consumption and body weight occurred in both sexes, accelerated with increasing log(DMH) dose, and were substantially more severe in groups fed 10% protein. A 5-mo study was subsequently performed with male mice fed 10 or 40% protein diets containing doses of 0, 15, 30, or 45 mg DMH-2HCl/kg diet. In this longer study, dose-related declines of food intake and body weight were also more pronounced with 10% protein. Histopathologic examination of samples from 29 organs/tissues revealed hepatic changes most commonly, and these were more severe at higher DMH levels. Lesions ranged from focal centrilobular hepatocellular necrosis to severe toxic hepatitis, associated with lobular disorganization and hepatocellular hypertrophy. Frequent dose-dependent lesions were also found in kidneys, adrenals, and heart. Renal changes included focal subcapsular fibrosis with atrophy, and hyperplasia of the tubular epithelium. Adrenal cortical hypertrophy was noted at the two highest DMH doses. Focal cardiac myocytolysis was also noted at high DMH doses. Renal damage occurred only rarely in the absence of liver pathology, and adrenal hypertrophy only rarely without renal damage. Cardiac myocytolysis was found in 14% of mice without hepatic, renal, or adrenal damage, but in 62% of those with lesions in each of those organs. No evidence of gastrointestinal toxicity was observed. Hepatic, renal, and adrenal lesions were more frequent and severe in mice fed the low-protein diet. The protective effect of high protein was DMH-dose dependent. The lower doses in these studies could be used to investigate effects of diet, cocarcinogens, or chemopreventative agents on carcinogenesis resulting from chronic, low-level dietary exposure to DMH.

The effects of two carcinogens benzo[a]pyrene (BP) and symmetrical 1,2-dimethylhydrazine dihydrochloride (DMH), on plasma amino acid concentrations and on excretion of lipids and nitrogenous metabolites were studied in 7- to 8-wk-old male and female B6C3F1 mice. BP and DMH were fed at concentrations of 0.3125 and 0.0225 g/kg, respectively, in purified diets containing 10 or 40% soybean protein. Nutritional balances were measured over a 7-d period after 7 d of acclimatization. Females excreted less urea and more NH3 than males. Urinary urea-nitrogen, NH3, allantoin, uric acid and total urinary nitrogen were consistently higher in mice fed 40% protein than in those fed 10% protein. The increases in total and NH3 nitrogen paralleled the increase in nitrogen intake. Nitrogen of urea rose more, while that of allantoin and uric acid rose less, than nitrogen intake. Fecal lipid excretion, as a percentage of intake, was consistently higher in mice fed the 40% protein diets than in mice fed 10% protein. Plasma glycine and branched-chain amino acids were higher, but citrulline was lower, when the 40% protein diet was fed. Body weight gain was higher when the 10% protein diet was fed with BP than without it, but BP made no apparent difference in weight gain when the 40% protein diet was fed. BP interacted with dietary protein to influence the excretion of nitrogenous metabolites. In addition, BP feeding produced numerous BP X sex and BP X protein interactions for plasma amino acid concentrations. Compared to controls, feed intake and weight gain were, respectively, 8 and 61% lower in DMH-fed animals during wk 1, but no differences in intake or weight gain were found during wk 2. In contrast to BP, DMH had no significant effects on urinary or fecal nitrogen metabolites, except that urinary uric acid (relative to nitrogen intake) was 9% higher in DMH-fed mice than in controls. DMH-fed mice had 43% higher serum glutamate and 6% lower glutamine than controls.

Over the past 150 years, our ability to produce and transform engineered materials has been responsible for our current high standards of living, especially in developed economies. However, we must carefully think of the effects our addiction to creating and using materials at this fast rate will have on the future generations. The way we currently make and use materials detrimentally affects the planet Earth, creating many severe environmental problems. It affects the next generations by putting in danger the future of the economy, energy, and climate. We are at the point where something must drastically change, and it must change now. We must create more sustainable materials alternatives using natural raw materials and inspiration from nature while making sure not to deplete important resources, i.e. in competition with the food chain supply. We must use less materials, eliminate the use of toxic materials and create a circular materials economy where reuse and recycle are priorities. We must develop sustainable methods for materials recycling and encourage design for disassembly. We must look across the whole materials life cycle from raw resources till end of life and apply thorough life cycle assessments (LCAs) based on reliable and relevant data to quantify sustainability. We need to seriously start thinking of where our future materials will come from and how could we track them, given that we are confronted with resource scarcity and geographical constrains. This is particularly important for the development of new and sustainable energy technologies, key to our transition to net zero. Currently ‘critical materials’ are central components of sustainable energy systems because they are the best performing. A few examples include the permanent magnets based on rare earth metals (Dy, Nd, Pr) used in wind turbines, Li and Co in Li-ion batteries, Pt and Ir in fuel cells and electrolysers, Si in solar cells just to mention a few. These materials are classified as ‘critical’ by the European Union and Department of Energy. Except in sustainable energy, materials are also key components in packaging, construction, and textile industry along with many other industrial sectors. This roadmap authored by prominent researchers working across disciplines in the very important field of sustainable materials is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the sustainable materials community. In compiling this roadmap, we hope to aid the development of the wider sustainable materials research community, providing a guide for academia, industry, government, and funding agencies in this critically important and rapidly developing research space which is key to future sustainability., The authors would like to thank The Faraday Institution ReLiB Project Grant Numbers FIRG005 and FIRG006, the UKRI Interdisciplinary Circular Economy Centre for Technology Metals (Met4Tech) Grant No. EP/V011855/1 and the EPSRC Critical Elements and Materials Network (CREAM) EP/R020140/1 for providing financial assistance for this research.