Investigational anabolic agents for the treatment of osteoporosis: an update on recent developments

Introduction: Teriparatide, a PTH analogue, was the first anabolic agent to be approved for the treatment of osteoporosis in 2002. Abaloparatide was also recently approved by the FDA. The need for other anabolic agents is still unmet.

Areas covered: In this review, we discuss target molecules and recent advances in the field of anabolic therapy for osteoporosis. PTH and PTHrP analogues binding to the PTH receptor and different routes of administration of teriparatide to avoid the burden of daily subcutaneous injections are discussed. We also review antibodies targeting suppressors of the Wnt pathway such as sclerostin and Dickopff-1.

Expert opinion: The development of alternative ways of administering PTH receptor ligands is a promising field, especially via the transdermal route. Other more promising molecules are still at very early stages of development. FDA recently requested more data on Romosozumab.     

The use of single chain Fv as targeting agents for immunoliposomes: an update on immunoliposomal drugs for cancer treatment

Importance of the field: Targeted liposomal drugs represent the next evolution of liposomal drug delivery in cancer treatment. In various preclinical cancer models, antibody-targeted PEGylated liposomal drugs have demonstrated superior therapeutic effects over their non-targeted counterparts. Single chain Fv (scFv) has gained popularity in recent years as the targeting agent of choice over traditional targeting agents such as monoclonal antibodies (mAb) and antibody fragments (e.g., Fab′).

Areas covered in this review: This review is focused mainly on advances in scFv-targeted liposomal drug delivery for the treatment of cancers, based on a survey of the recent literature, and on experiments done in a murine model of human B-lymphoma, using anti-CD19 targeted liposomes targeted with whole mAb, Fab′ fragments and scFv fragments.

What the reader will gain: This review examines the recent advances in PEGylated immunoliposomal drug delivery, focusing on scFv fragments as targeting agents, in comparison with Fab′ and mAb.

Take home message: For clinical development, scFv are potentially preferred targeting agents for PEGylated liposomes over mAb and Fab′, owing to factors such as decreased immunogenicity, and pharmacokinetics/biodistribution profiles that are similar to non-targeted PEGylated (Stealth^®) liposomes.     

Characteristics and consequences of heroin use among older adults in the United States: a review of the literature, treatment implications, and recommendations for further research

This review reports on the results of a comprehensive literature search of studies examining the physical and mental health characteristics of older adults in the United States who use heroin. Multiple databases were searched for papers meeting the inclusion criteria of heroin users who were age 50 years or older. A total of 14 articles covering 9 different studies met the review inclusion criteria. All of the studies were convenience samples, and seven of the nine studies (77.8%) were entirely drawn from substance abuse treatment programs, primarily methadone maintenance programs. Findings from the qualitative studies suggest that the marginalization of older heroin users was a predominant experience that impacted the intent to seek treatment as well as treatment retention. While articles reported high levels of physical and psychological/psychiatric comorbidities with substance misuse, research on heroin use and methadone treatment among older adults is scant and the quantitative findings are inconsistent. The articles reviewed in this study demonstrate that the needs of this population will be significant, yet the development of appropriate interventions and treatment for older adult heroin users will be contingent on empirical research that adequately describes mental and physical health problems.     

In vivo and in vitro investigations on biological effects of aromatic bis-(2-chloroethyl)amino-bisphosphonic acids,new agents proposed for chemotherapy of bone tumors: cytostatic activity in rat osteosarcoma; toxicity and genotoxicity in liver and bone marrow; mutagenicity in S. Typhimurium

Summary Two new aromatic bis-(2-chloroethyl)-amino derivatives (BCMP and BAD) which are linked to osteotropic bisphosphonates were investigated for their therapeutical efficacy in rat osteosarcoma. Furthermore their genotoxic potential in vitro was determined in S. typhimurium and in mammalian cells. Finally, parameters for toxicity and genotoxicity were determined in liver and bone marrow cells following in vivo treatment. It was shown that BAD was of higher therapeutic effectiveness than BCMP. Both compounds induced approximately a two fold increase of his⁺ revertants in S. typhimurium TA1535 following metabolic activation by subcellular liver fractions. Both compounds also induced amplification of SV40 DNA in SV40 transformed cells (CO631). This endpoint may be of importance for acquired resistancy of cells during therapy. DNA-single strand breaks were induced by BCMP but not by BAD in liver cells and CO631 cell line. Following in vivo treatment BCMP was of higher genotoxic activity in liver cells than BAD. In comparison, genotoxicity of both compounds was much lower in bone marrow cells than in liver cells. BCMP was again more potent than BAD in inducing DNA single strand breaks, whereas BAD was more toxic. The higher therapeutic efficacy of BAD together with its lower genotoxic properties makes this compound superior to BCMP as a candidate for applied chemotherapy in humans.