Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Gay Community Involvement and Condomless Anal Sex Among Sexual Minority Men in the USA

Archives of Sexual Behavior - Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective...     

Electrical stimulation of osteonecrosis of the femoral head

Osteonecrosis of the femoral head in the adult is a progressive condition that, if untreated, usually results in femoral head collapse and secondary osteoarthritis. The experimental application of electrical and electromagnetic fields has been shown to favorably affect a number of biological processes pertinent to osteonecrosis of the femoral head and has led to several clinical trials. The condition has been treated by the application of electrical fields invasively by the surgical implantation of electrodes within the femoral head and noninvasively by capacitative or inductive coupling. This review describes results in osteonecrosis of the femoral head with these therapeutic techniques. Stimulation by means of inductive coupling with pulsed magnetic fields seems to be the most promising technique studied so far, but the optimal signal characteristics and device design are not yet known.     

Positive and negative regulation of cellular sensitivity to anti-cancer drugs by FGF-2.

The development of resistance to chemotherapy by tumor cells remains a constant limitation to the treatment of cancer. Over the last several years, fibroblast growth factor-2 (FGF-2) has emerged as a growth factor that is capable of modifying the sensitivity of normal and tumor cells to anti-cancer drugs. FGF-2 can produce both drug resistance and drug sensitization in different cell types treated with a variety of cytotoxic agents. An understanding of the differential cellular trafficking and biological activities of the multiple FGF-2 isoforms will help in determining the circumstances under which FGF-2 acts to inhibit versus potentiate drug action. Recent advances suggest that expression of FGF-2 in tumor cells is involved with loss of response to chemotherapy in vivo. Thus, the manipulation of FGF-2 activities to increase the effectiveness of chemotherapeutic agents may have important clinical implications.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.