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A double-blind, placebo-controlled study on 21 postmenopausal osteoporotic women was performed in order to assess the effects of 1 year estrogen therapy (Premarin, 1.25 mg/day) on bone mass, intestinal calcium absorption, and mineral metabolism. Bone mineral content (BMC), measured by dual photon absorptiometry on the vertebral bodies and the femoral shaft, increased in both areas, but the changes were more evident at the former site, which is predominantly trabecular (+8.3%, P less than 0.05), than at the latter, which is mainly cortical (+2.6%, P less than 0.05). An improvement of intestinal calcium absorption was also detected at the end of the study (P less than 0.05) in the estrogen-treated group. Parameters of bone metabolism showed a decrease in hydroxyproline/creatinine ratio and osteocalcin, an increase in calcitonin, and no significant changes in parathyroid hormone (PTH) and alkaline phosphatase. Serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3) levels increased after estrogen therapy, whereas 25-hydroxycholecalciferol (25OHD3) remained stable during the study period. Renal 25-hydroxyvitamin D 1 alpha-hydroxylase reserve, assessed by the PTH-stimulation test, showed a more rapid response in producing a 1,25(OH)2D3 peak in the estrogen-treated patients compared with the control subjects. However, estrogens did not induce an absolute improvement in the secretory reserve. This study demonstrates that 1 year treatment with estrogens improves both intestinal calcium absorption and BMC in postmenopausal osteoporotic women. The latter effect appears to be induced by an inhibition of bone resorption, associated to an increased secretion of calcitonin, whereas vitamin D metabolites do not seem to contribute substantially to the mediation of estrogen action on bone.

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Estrogen treatment improves calcium malabsorption induced by surgical or natural menopause, but the mechanisms involved are still under debate, with both increased production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and improved peripheral responsiveness to the steroid having been proposed. To address this issue, we studied the effect of short term administration of 1,25-(OH)2D3 (1 microgram/day for 7 days) on intestinal fractional absorption of 47Ca (47Ca FA) and vertebral bone density, measured by dual photon absorptiometry, in 14 premenopausal women (aged 31-50 yr) before and 6 months after oophorectomy. After surgery, patients were randomly allocated to a 6-month treatment with either conjugated estrogens (0.625 mg/day; n = 7) or placebo (n = 7). Oophorectomy caused a decrease in both basal 47Ca FA (-40.8 +/- 23.4%; P = 0.004) and vertebral bone density (-7.21 +/- 1.20%; P less than 0.001) in the placebo group. Estrogen replacement prevented these changes and increased basal serum 1,25-(OH)2D3 (+10.3 +/- 10.9%; P = 0.047), whereas a detectable but not significant decrease was observed in the control group (-8.8 +/- 10.5%; P = 0.07). Assessment of 47Ca FA before and after 1,25-(OH)2D3 administration revealed a similar degree of responsiveness to the steroid in the estrogen-treated women before and at the end of the study period (45.8 +/- 6.9% vs. 42.9% +/- 14.9% from basal, respectively; P = 0.142), but a blunted response to 1,25-(OH)2D3 was observed in the placebo group at 6 months (27.9 +/- 17.7%) compared to the result obtained before surgery (36.7 +/- 9.1%; P = 0.032). Multifactor analysis of variance revealed that the effects of estrogen and 1,25-(OH)2D3 on 47Ca FA were independent of basal serum 1,25-(OH)2D3 levels. On the other hand, calcitriol administration increased serum 1,25-(OH)2D3 to a similar extent before and 6 months after surgery in the placebo group (24.2 +/- 18.3% vs. 34.7 +/- 16.7% from basal, respectively; P = 0.484) as well as in the estrogen-treated women (34.2 +/- 17.2% vs. 26.6 +/- 15.45%; P = 0.302). The significant impairment of 1,25-(OH)2D3 stimulation of 47Ca FA in spite of increased levels of circulating 1,25-(OH)2D3 in the untreated women is suggestive of an end-organ resistance to the vitamin D metabolite in a hypoestrogenic condition, which can be prevented by hormone replacement, and supports the hypothesis of a vitamin D-independent action of estrogen on intestinal calcium absorption.

The results of new archival research, compared with some epistles of Blessed Giovanni Colombini, allowed to frame the mystical experience of his cousin Caterina Colombini, which matured in the Sixties of the fourteenth century, in a situation of serious breakdown with his family, caused by patrimonial reasons. Caterina succeeded, also with the help of some friends of her cousin, to free herself from the family context and to constitute the first community of Gesuate, so-called because they observed the same way of life as the Gesuati, then in 1371 to equip this congregation with a residence purchased with her own money in the Sienese district of Vallepiatta and finally to submit it to the protection and jurisdiction of the female Benedictine monastery of Saints Abondio and Abondanzio near Siena. Thus a new female congregation was born, that also spread to other cities in Italy, but it did not turn into a religious order, while avoiding the accusation of heresy for “beguinage”.

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Of the 147 PDB patients, 22 (15%) had at least one other family member affected, 19 (13%) reported one family member with suspected features of PDB, and 106 (72%) were classified as sporadic PDB. Even though we observed a reduced clinical severity of PDB with respect to other populations (mean number of affected sites, 2.2 +/- 1.6), we did not find any evidence of a decreased severity of the disease over time. We also found an association of PDB with animal contact (odds ratio [OR], 2.22; p < 0.0005) and a significant prevalence of PDB in rural versus urban districts (OR, 2.42; p < 0.0005). Osteoarthritis (45%), fractures (14%), hearing loss (14%), and valvular calcifications (15%) were the most observed complications. Interestingly, the geographical distribution of PDB showed a concentration of cases in rural areas of Campania and Tuscany. These areas may indicate local clustering of PDB cases in Italy, similar to that observed in other countries.