Correction: Glucocorticoid-Induced Osteoporosis (GIOP).

[This corrects the article DOI: 10.1007/s43465-023-01037-8.].

Osteoporosis in Asthma and COPD.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are principally lifestyle related chronic inflammatory airway disease. They are globally associated with various systemic comorbidities and mortality. Osteoporosis is the common associated metabolic bone disease with respiratory disturbances, which affect the prognosis and increase mortality and morbidity in the patients. Apart from OSTEOPOROSIS, exhaustive attention has been paid towards other associated systemic comorbidities like cardiovascular diseases, cerebrovascular diseases, metabolic syndrome, malnutrition, skeletal muscle dysfunction (sarcopenia), anxiety, depression and so on (Iheanacho et al. in Int J Chronic Obstr Pulm Dis 15:439-460, 2020; Singh et al. in Eur Respir J 53:1900164, 2019). Osteoporosis is a significant extrapulmonary manifestation in asthma and COPD, which are grossly neglected and inadequately treated. The comorbidities have significant impact in terms of morbidity, mortality and economic burden in asthma and COPD patients, hence management of asthma and COPD should comprise thorough management, as this will also have an impact on the outcome of these patients. Various risk factors such as smoking, systemic inflammation, vitamin deficiency, and the use of oral or inhaled corticosteroid are responsible for osteoporosis in patients with asthma and COPD. The presence of osteoporosis in patients with asthma and COPD is invariably asymptomatic unless complicated by fragility fractures, therefore, it is necessary to explore the pathogenesis of osteoporosis in asthma and COPD and special attention is to be paid for early recognition of patients at high risk for osteoporosis in these patients. This chapter is focussed on osteoporosis as an extrapulmonary manifestation of asthma and COPD with an emphasis on the pathogenesis, risk factor, potential mechanism of osteoporosis, diagnosis, and prevention with passing reference to treatment as well in asthma and COPD patients.

Pain Management in Osteoporosis.

The most prevalent metabolic bone disease, osteoporosis, is characterized by a decrease in bone mineral density and alterations to the bone's microstructure, both of which can result in fragility fractures. It affects a significant section of the population. Acute or chronic pain from these fractures is typical in elderly adults with other coexisting conditions. Since the antiresorptive medication only partially reduces pain, other analgesics are required for effective pain management. NSAIDs or selective COX-2 inhibitors can reduce acute pain, but persistent neuropathic pain is difficult to manage with these drugs. Opioids have their adverse effects and safety concerns, although they can be used to address acute or chronic pain. Hence, a multifaceted approach is to be implemented, including pharmacological and nonpharmacological therapy and surgical treatment in a selected number of cases. This chapter briefly describes the etiology of pain, its mechanism, and pain management in osteoporotic patients.

Glucocorticoid-Induced Osteoporosis (GIOP).

Use of glucocorticoid in various diseases including rheumatology and respiratory diseases is on the rise because of its prompt beneficial effects. This culminates in osteoporosis and fragility fractures. Judicious use of glucocorticoid hence calls for attention with regard to the dose schedule, route of administration and accompanying enhancing factors. Institution of proper therapeutic management as per WHO risk stratification with anabolic and/or resorptive drugs like bisphosphonates, teriparatide or denosumab is necessary to prevent the eventuality of fragility fractures. Even otherwise, knowledge of glucocorticoid, its metabolism, various dose schedules, adverse effects are areas worth discussing.

CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation.

The matricellular protein CCN5/WISP-2 represents a promising target in triple-negative breast cancer (TNBC) because treatment or induced activation of CCN5 in TNBC cells promotes cell growth arrest at the G0/G1 phase, reduces cell proliferation and delays tumor growth in the xenograft model. Our studies found that the p27(Kip1) tumor suppressor protein is upregulated and relocalized to the nucleus from cytoplasm by CCN5 in these cells and that these two events (upregulation and relocalization of p27(Kip1)) are critical for CCN5-induced growth inhibition of TNBC cells. In the absence of CCN5, p27(Kip1) resides mostly in the cytoplasm, which is associated with the aggressive nature of cancer cells. Mechanistically, CCN5 inhibits Skp2 expression, which seems to stabilize the p27(Kip1) protein in these cells. On the other hand, CCN5 also recruits FOXO3a to mediate the transcriptional regulation of p27(Kip1). The recruitment of FOXO3a is achieved by the induction of its expression and activity through shifting from cytoplasm to the nucleus. Our data indicate that CCN5 blocks PI3K/AKT signaling to dephosphorylate at S318, S253 and Thr32 in FOXO3a for nuclear relocalization and activation of FOXO3a. Moreover, inhibition of α6ß1 receptors diminishes CCN5 action on p27(Kip1) in TNBC cells. Collectively, these data suggest that CCN5 effectively inhibits TNBC growth through the accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation, and thus, activation of CCN5 may have the therapeutic potential to kill TNBC.

Citrobacter rodentium espB is necessary for signal transduction and for infection of laboratory mice.

Citrobacter rodentium is the causative agent of transmissible murine colonic hyperplasia and contains a locus of enterocyte effacement (LEE) similar to that found in enteropathogenic Escherichia coli (EPEC). EPEC espB is necessary for intimate attachment and signal transduction between EPEC and cultured cell monolayers. Mice challenged with wild-type C. rodentium develop a mucosal immunoglobulin A response to EspB. In this study, C. rodentium espB has been cloned and its nucleotide sequence has been determined. C. rodentium espB was found to have 90% identity to EPEC espB. A nonpolar insertion mutation in C. rodentium espB was constructed and used to replace the chromosomal wild-type allele. The C. rodentium espB mutant exhibited reduced cell association and had no detectable fluorescent actin staining activity on cultured cell monolayers. The C. rodentium espB mutant also failed to colonize laboratory mice following experimental inoculation. The espB mutation could be complemented with a plasmid-encoded copy of the gene, which restored both cell association and fluorescent actin staining activity, as well as the ability to colonize laboratory mice. These studies indicate that espB is necessary for signal transduction and for colonization of laboratory mice by C. rodentium.

Proliferative enterocolitis associated with dual infection with enteropathogenic Escherichia coli and Lawsonia intracellularis in rabbits.

Both enteropathogenic Escherichia coli (EPEC) and an obligate intracellular bacterium, previously referred to as an intracellular Campylobacter-like organism and now designated Lawsonia intracellularis, have been reported as causes of enterocolitis in rabbits. An outbreak of enterocolitis in a group of rabbits, characterized by an unusually high rate of mortality, was found to be associated with dual infection with EPEC and L. intracellularis. The EPEC strain was found to have eaeA gene homology but was negative for afrA homology. The absence of the afrA gene, which encodes the structural subunit for the AF/R1 pilus, indicates that this rabbit EPEC strain is distinct from the prototypic RDEC-1 strain. This finding suggests that rabbit EPEC strains widely reported in Western Europe, which lack AF/R1 pili, are also present in rabbits in the United States. Dual infection with these two pathogens in rabbits has not been previously reported and may have contributed to the unusually high mortality observed in this outbreak.

Quantitative effect of family planning programme in India (1965-76).

PIP: The objective of this discussion is to determine how much India's fertility decline has occurred due to acceptance of all birth control methods combined and separately over the 1965-75 period. Age distribution of the conventional contraceptive users was assumed to be the same as that of IUD acceptors, and it was also assumed that the age distribution of sterilization acceptors, IUD users, and conventional contraceptives remains constant over the 1965-75 period. Fertility of the acceptors was taken as the same as that of nonacceptors. Wife's age was 5 years less than that of her husband. Level of mortality over the 1955-75 period was assumed to be constant. Use effectiveness of sterilization was 100%, IUD, 95% and conventional contraceptives 60%. The procedure for obtaining the annual performance of reduction in fertility level due to the family planning program involved 3 steps: estimation of the number of couples currently protected due to the practice of various family planning methods; conversion of all the currently protected couples into standard couples; and calculation of percentage of standard couples protected and percentage of reduction in birthrate. It was observed that the standard couples protected by the family planning program in the early reproductive age group were less, where the fertility rate was high as compared to the older age group. In the case of sterilization the percentage reduction in birthrate, during the 1st few years after 1965 was not so much, but the percentage reduction was significant as the program gained momentum from 1968-73. The percentage reduction in birthrate due to sterilization was as follows: 1966-67, 2.049; 1967-68, 2.660; 1968-69, 4.657; 1969-70, 6.289; 1970-71, 7.509; 1971-72, 8.524; 1972-73, 10.280; 1973-74, 13.037; 1974-75, 13.221; and 1975, 13.823. A cause for the IUD decrease from year to year might be the inadequate follow-up care after insertion. Overall, the number of standard couples protected by the family planning program indicated that the program had reduced the birthrate by 17.97% in 1975 against 3.404% in 1966.^ieng

"T"-osteotomy of the calcaneum.

The relative length and height of the lateral and medial walls of the calcaneum probably govern the production and persistence of structural hindfoot deformity, forefoot supination and adduction, and pronation and abduction. Anatomical restoration of the proportions of the calcaneal walls forms the basis of the T-osteotomy of the calcaneum. We have undertaken this operation on 72 feet in 60 patients for cavovarus deformity with forefoot adduction. The calcaneum is approached from the lateral side and the T-shaped osteotomy is performed through the body, the vertical limb being 1 to 1.5 cm behind and parallel to the calcaneo-cuboid joint. The horizontal limb starts from the centre of the vertical cut and ends above the attachment of the tendo achillis. The postero-inferior segment is pushed out correcting the heel varus and at the same time broadening the heel. The forefoot is manipulated downwards and outwards to correct the residual cavus and the adduction and supination of the forefoot. The over-all results, with an average follow-up of 3.7 years, have been satisfactory.