High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes.

PURPOSE: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. METHODS: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. RESULTS: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9-31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. CONCLUSIONS: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.

Persistence with denosumab therapy in women affected by osteoporosis with fragility fractures: a multicenter observational real practice study in Italy.

BACKGROUND: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. AIM: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. MATERIAL/SUBJECTS AND METHODS: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy. We included women with a diagnosis of post-menopausal osteoporosis, aged >50 years, able to obtain a prescription according to the Italian reimbursement criteria in force during the study period for anti-osteoporotic pharmacological treatment. They initiated a treatment with subcutaneous denosumab (Prolia®) 60 mg/every 6 months between November 2011 and May 2016. Women who had received aromatase inhibitors were excluded. Patients were assessed at baseline and every 6 months for all treatment length. Persistence data were evaluated for a total of 36 months. RESULTS: Eight hundred seventy women were enrolled; mean aged 70 years, with a mean body mass index of 24.8 ± 4.1 kg/m2. At the Dual-energy X-ray absorptiometry assessment, the mean lumbar spine T-score was -2.76 ± 1.14 standard deviations (SD) and the mean femoral neck T-score was -2.49 ± 0.80 SD. During the study, the total persistence was 91.4%. Total dropouts were 75 (8.6%), higher within the initial 6-month period of treatment. CONCLUSIONS: Persistence to denosumab treatment in our observational real practice study was very high. These results suggest that factors such as frequency of visits, pharmacological schedule, and opportunity to call the doctor might play an important role in the persistence and adherence to treatment to obtain maximum therapeutic effect and avoid further fragility fractures.

Bone damage in type 2 diabetes mellitus.

This review focuses on the mechanisms determining bone fragility in patients with type 2 diabetes mellitus (T2DM). Despite bone mineral density (BMD) is usually normal or more often increased in these patients, fracture incidence is high, probably because of altered bone "quality". The latter seems to depend on several, only partly elucidated, mechanisms, such as the increased skeletal content of advanced glycation end-products causing collagen deterioration, the altered differentiation of bone osteogenic cells, the altered bone turnover and micro-architecture. Disease duration, its severity and metabolic control, the type of therapy, the presence or absence of complications, as like as the other known predictors for falls, are all relevant contributing factors affecting fracture risk in T2DM. In these patients the estimate of fracture risk in the everyday clinical practice may be challenging, due to the lower predictive capacity of both BMD and risk factors-based algorithms (e.g. FRAX).

Effect of gender and geographic location on the expression of primary hyperparathyroidism.

BACKGROUND: The effect of gender on the expression of primary hyperparathyroidism (PHPT) is not well characterized. AIM: We therefore evaluated two Caucasian populations (US and Italian) of men and women with PHPT, matched for age and body mass index (BMI), in a cross-sectional retrospective observational study. METHODS: We studied 74 US (23 men) and 126 Italian (42 men) patients evaluating main biochemical indices of the disease and bone mineral density (BMD) at the spine and proximal femur. RESULTS: Mean serum calcium levels were higher both in Italian men compared to women (11.7 ± 1.22 mg/dl and 11.1 ± 0.83, p<0.01) and in Italian compared to US patients (11.3 ± 1.01 and 10.8 ± 0.58, p<0.001), with similar results for the serum ionized calcium. Mean serum PTH levels were not different either between the genders or between the countries. After controlling for BMI, the mean BMD at both the femoral neck and total hip in females US patients was significantly higher compared with Italian female patients. CONCLUSION: Despite similar levels of circulating PTH, Italian patients have more pronounced effects of the disease as assessed by serum calcium and a more significant cortical involvement in women as assessed by BMD.

Effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength: a study in young women.

BACKGROUND: The effect of a single large oral dose of vitamin D on muscle function in young people with vitamin D deficiency has not been investigated so far. AIM: We evaluated the effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength. SUBJECTS AND METHODS: Eighteen young women with vitamin D deficiency received a single oral dose of 600,000 IU of cholecalciferol. We evaluated changes in maximal voluntary contraction (MVC) and speed of contraction (S) in response to cholecalciferol by using an hand held dynamometer at 3, 15, 30, 60 and 90 days, compared to baseline. RESULTS: We observed no significant change in MVC and S values, a significant increase of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and a significant decrease in serum parathyroid hormone (PTH) (p<0.001 for all). A significant correlation was found between MVC and S and serum phosphorus (P) after supplementation (p<0.02 and p<0.05, respectively). Conversely, we observed no association between the parameters of muscle strength and 25(OH)D, ionized calcium (Ca2+), PTH and 1,25(OH)2D. CONCLUSIONS: A single dose of 600,000 IU of cholecalciferol does not directly enhance handgrip strength in young women with vitamin D deficiency. More studies are needed on the indirect effect of the hormone on muscle.

Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin.

OBJECTIVE: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS. PATIENTS AND METHODS: One-hundred- seventeen successfully treated first STEMI (age 63.8±12.5 yrs, 70% men) and 64 AS (age 80.3±6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up. RESULTS: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7±2.1 vs. 11.3±1.7, p=ns). GLS cut-off ≤12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS ≤12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (χ2 6.691 vs. 1.364, p=0.010). CONCLUSIONS: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

Serum sclerostin levels decline in post-menopausal women with osteoporosis following treatment with intermittent parathyroid hormone.

OBJECTIVE: This study was carried out in order to evaluate the effect of 18-month treatment with PTH (1-34) or PTH (1-84) on serum sclerostin levels in humans. SUBJECTS AND METHODS: We investigated 10 women with severe osteoporosis, previously treated with alendronate and 20 untreated osteoporotic women. Subjects with severe osteoporosis were randomly divided into 2 groups of 5 patients each; the first group was treated with 20 µg of PTH (1-34) and the second one with 100 µg of PTH (1-84) according to an open-label design. Fasting blood samples were collected at baseline and at 2, 4, and 24 h after hormone administration. The same protocol was followed at month 1, 6, 12, 18. Serum sclerostin levels were measured at each time point by a sandwich-type enzyme-linked immunosorbent assay. RESULTS: Basal serum sclerostin levels were not significantly different between patients previously treated with alendronate and those never treated. No significant acute change of serum sclerostin levels was observed after PTH administration. Fitting a mixed effect regression model, we found a significant time effect (p=0.0012) using the sclerostin level as the response variable and the month of drug administration as a single covariate. Treatment with both PTH molecules induced a monthly mean reduction of sclerostin levels of 0.1956 pmol/l. CONCLUSIONS: Our results indicate that long-term therapy with PTH (1-34) or PTH (1-84) in women with osteoporosis previously treated with alendronate is associated with a reduction in circulating sclerostin levels. This is a putative mechanism through which PTH performs its anabolic action.

Chronic constipation in hypercalcemic patients with primary hyperparathyroidism.

BACKGROUND: Chronic constipation (C), among gastrointestinal symptoms, is commonly associated with primary hyperparathyroidism (PHPT) and probably attributable to hypercalcemia. OBJECTIVE OF THE STUDY: To evaluate in patients affected with PHPT the prevalence of C utilizing a validated questionnaire and the current prevalence of C compared to that observed in the past and to evaluate the relationship between C and the severity of PHPT. METHODS: 55 outpatients affected with PHPT, admitted to our Department of Internal Medicine and Medical Specialities in the years (2006-2009) were studied (group 1: 50 postmenopausal women and 5 men, mean age 61.9 +/- 9.4 years), together with 55 sex and age matched controls (group 2). Also considered were a group of PHPT patients observed, in the same ambulatory, during the years '70-'80 (group 3). A questionnaire, Rome II criteria, was administered and used to define C, whereas only anamneses were used to define C in group 3. RESULTS: The prevalence of C in patients with PHPT was 21.8% in group 1 vs 12.7% in group 2 (n.s.) and 32.7% in group 3. There is a decreasing trend in the prevalence of C in patients with PHPT as observed from 1970-89 to 2006-2009 (p < 0.05). The reduction of C was associated together with a significant reduction in the serum calcium level (p < 0.001). The presence of C vs its absence in patients with PHPT is characterized by higher values of calcemia (p < 0.001), ionized calcium (p < 0.001), and parathyroid hormone (p = 0.019). CONCLUSION: The actual prevalence of C in patients with PHPT is not significantly different from that found in the control group and is decreasing with respect to the past years. Moreover, C seems to be associated with the severity of the disease rather than with the diagnosis of PHPT per se.

Vertebral morphometry by dual-energy X-ray absorptiometry (DXA) for osteoporotic vertebral fractures assessment (VFA).

PURPOSE: This study was done to evaluate the diagnostic accuracy of dual-energy X-ray absorptiometry (DXA) compared with conventional radiography for identifying vertebral fractures. MATERIALS AND METHODS: A total of 930 postmenopausal women underwent conventional radiography and DXA imaging of the spine. The images were evaluated by two expert skeletal radiologists using the semiquantitative (SQ) method for conventional radiography and the morphometric vertebral fracture assessment (VFA) for DXA. RESULTS: The SQ method for radiography (SQ-Rx) analysed 99.1% of vertebrae, identifying 442 vertebral fractures; VFA analysed 97.5% vertebrae, detecting 420 vertebral fractures. Agreement between SQ-Rx and VFA reached 98.76%, and the κ-score was 0.96 [95% confidence interval (CI), 0.95-0.98]. Assessing the grading of vertebral fractures, agreement reached 97.5% and the κ-score was 0.841 (95% CI, 0.821-0.891). Considering SQ-Rx method as "gold standard", VFA had a sensitivity of 97.85 % and a specificity of 99.81%. The negative (NPV) and positive (PPV) predictive value for VFA were 99.83 % and 98.15%, respectively. Fractures were identified in 251 (27 %) and 242 (26 %) of patients on SQ-Rx and VFA, respectively. On a per-patient basis, the agreement between the two methods was 97% and the κ-score was 0.95 (95% CI, 0.920-0.968). The diagnostic parameters for VFA were 97.23% sensitivity, 98.86% specificity, 97.60% PPV and 98.84% NPV. CONCLUSIONS: This study demonstrated that VFA with DXA may reach a high level of accuracy for diagnosing vertebral fractures, suggesting that VFA should be introduced in the screening of individuals with a risk of osteoporosis and in the follow-up of osteoporotic patients receiving treatment.

Sporadic and hereditary primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, particularly frequent in post-menopausal women. It is characterized by hypercalcemia with inappropriately high spontaneous plasma PTH. Singlegland adenoma is the most common cause (75- 85%). PHPT is usually a sporadic disease but in approximately <5% of cases, a familial hyperparathyroid syndrome is diagnosed. Familial hyperparathyroidism is a clinically and genetically heterogeneous group of disorders including: multiple endocrine neoplasia (MEN) type 1, MEN type 2A, MEN4, benign familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, hyperparathyroidism-jaw tumor syndrome, and familial isolated hyperparathyroidism. These syndromes show mendelian inheritance patterns and the main genes for most of them have been defined. The classic form of PHPT, which presents with hypercalcemia, kidney stones, and bone disease, is no longer common. Currently, there is an increasing interest in the subtle manifestations of PHPT, particularly the cardiovascular and neuropsychiatric manifestations. Parathyroidectomy is the definitive cure for PHPT even though patients with the asymptomatic form of the disease can be followed conservatively.

[Guidelines on prevention and treatment of vitamin D deficiency. Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)]. / Linee guida su prevenzione e trattamento dell'ipovitaminosi D con colecalciferolo. SIOMMMS.

The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has elaborated the following guidelines about the definition, prevention and treatment of inadequate vitamin D status. The highlights are presented here. Daily vitamin D allowance ranges from 1,500 IU (healthy adults) to 2,300 IU (elderly with low calcium intake). Since the average Italian diet includes around 300 IU/day, subjects with no effective sun exposure should be supplemented with 1,200-2,000 IU vitamin D per day. The serum 25-hydroxy-vitamin D [25(OH)D] levels represents the most accurate way to assess vitamin D repletion, even though there are still no standardized assay methods. Conditions of "deficiency" and "insufficiency" are defined by the following ranges of 25(OH)D levels: less than 20 ng/ml and 20-30 ng/ml, respectively. In Italy, approximately 50% of young healthy subjects have vitamin D insufficiency during the winter months. The prevalence of deficiency increases with ageing, affecting almost all elderly subjects not on vitamin D supplements. When a condition of deficiency has been identified, a cumulative dose of 300,000-1,000,000 IU, over 1-4 weeks is recommended. In subjects recently treated for deficiency-insufficiency, a maintenance dose of 800-2,000 IU/day (or weekly equivalent) is recommended. In patients on daily doses over 1,000 IU, 25(OH)D levels should be checked regularly (e.g. once every two years). The highest tolerated daily dose has been identified as 4,000 IU/day. Vitamin D supplementation should be carefully monitored in patients at higher risk of vitamin D intoxication (granulomatosis) or with primary hyperparathyroidism. In pregnant women, vitamin D supplements should be given as in non-pregnant women, but bolus administration (i.e.: single dose >25,000 IU) should be avoided.

Skeletal turnover, bone mineral density, and fractures in male chronic abusers of alcohol.

BACKGROUND: Chronic alcohol abuse is a risk factor for osteoporosis and fractures, whose pathogenesis is still unclear. We investigated the influence of alcoholism and other risk factors on calcium and skeletal metabolism, bone mineral density (BMD), and fractures. MATERIALS AND METHODS: In 51 chronic male alcoholics without liver failure and 31 healthy controls, serum total and ionised calcium, phosphate, creatinine, 25-hydroxy vitamin D (25OHD), PTH, total (ALP) and bone-specific (BALP) alkaline phosphatase, osteocalcin (BGP), carboxy-terminal telopeptide of type I collagen (beta-CTx), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were assessed. In patients only, we also measured serum testosterone, 17-beta estradiol, LH, and IGF-I. BMD was measured by dual energy x-ray absorptiometry at lumbar spine (LS-) and femur [neck (FN-) and total hip (TF-)]. Vertebral fractures were identified by a semiquantitative method on thoraco-lumbar spine x-ray, non-vertebral fractures (as life-style factors) by history. RESULTS: Alcoholics were leaner, had significantly higher ALP and BALP, and lower BGP and 25OHD levels than controls. No significant difference in other calcium and bone metabolism parameters was found. OPG/RANKL ratio was significantly higher in alcoholics. Beta-CTx negatively correlated with abuse duration. OPG positively correlated with daily alcohol assumption and with indexes of liver cytolysis. Though LS-, FN- and TF-BMD of alcoholics and controls did not significantly differ, patients had a much higher prevalence of vertebral fractures. The same was found considering both vertebral and non-vertebral fractures. CONCLUSIONS: Ethanol-induced skeletal damage seems mainly dependent on negative effects on bone formation. Lifestyle factors and traumas likely contribute to the high fracture incidence of alcohol abusers, independently of BMD.

Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome.

PURPOSE: To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT). METHODS: Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT. RESULTS: Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship. CONCLUSIONS: In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

[Primary hyperparathyroidism]. / Iperparatiroidismo primitivo.

Primary hyperparathyroidism (PHPT) is characterized by excessive PTH secretion in respect to calcium homeostasis needs, due to parathyroid adenoma (80% of cases), hyperplasia (15-20%), or carcinoma (1-2%). In familial forms of PHPT, several mutations have an established role: menin gene for MEN type 1, RET for MEN type 2a, calcium-sensing receptor gene for familial hypocalciuric hypercalcemia, parafibromin gene for PHPT-jaw tumour and carcinoma. Etiology of sporadic adenomas (80% of PHPT cases) is less defined, being most commonly found a mutation of menin gene or activation of PRAD1 oncogene. In recent years, the classical features of the disease became less common. Typically, bone involvement is now represented by a reduced bone mass at skeletal sites more rich in cortical tissue. Prominently trabecular skeletal sites are relatively spared, because of the anabolic effects of a slight PTH excess on trabecular tissue. PHPT patients may have increased fracture risk, though it is not clear why bone damage is more severe in a subgroup of patients. Clinical features of hypercalcemia may be fatigue, anorexia, thirst, and polyuria. Vague neurological and psychiatric symptoms, such as weakness, anxiety, depression, paresthesias, and muscular cramps may ameliorate after parathyroidectomy. Recent reports indicate increased cardiovascular mortality in PHPT patients. Diagnosis is based on the detection of hypercalcemia, together with inappropriately high serum PTH levels. Preoperative localization of the diseased glands is mandatory in persistent or recurrent PHPT, as like as when minimally invasive surgery is planned. High resolution ultrasonography and SPECT double-phase 99m Tc-sestamibi scintigraphy are the most commonly employed techniques. Intraoperatory PTH assay may confirm successful surgery when serum concentrations decrease more than 50%. Surgical therapy is indicated in patients with renal or skeletal complications, such as in those with previous parathyrotoxic crisis. Many surgeons in recent years adopted minimally invasive parathyroidectomy. Medical treatment is an option for patients unwilling or unfitted for surgery because of severe concomitant diseases. Employed therapy includes estrogens, SERMs, bisphosphonates and calcimimetics.

[Paraneoplastic syndromes: a review]. / Le sindromi paraneoplastiche: revisione critica della letteratura.

Modern oncology often obtains good results against earlier neoplasms, whilst it's still in difficulties against the advanced ones. The knowledge of paraneoplastic syndromes is crucial both to cure patients and to do an earlier diagnosis. When we recognize a paraneoplastic syndrome that comes before the clinic beginning of a neoplasm, perhaps we save a life. This review discusses all the main paraneoplastic syndromes, focusing mainly on their clinical aspect and reminding the most commonly associated cancers.

Parathyroid storm: immediate recognition and pathophysiological considerations.

A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling.

Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery.

This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 +/- 3.1 SEM years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 +/- 27 SEM micrograms/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.

The effects of oophorectomy on skeletal metabolism.

The effects of oophorectomy on the biological indices of bone remodelling and the time-course of their changes are described. In the first few months following surgical menopause the measurement of the markers of bone remodelling indicates that the increase in osteogenesis is delayed compared with that of bone resorption; this prevalence of destruction over new bone deposition justifies the deficiency of skeletal balance, shortly after acute oestrogen deficiency. The changes in bone remodelling are accompanied by an increase in serum calcium while serum immunoreactive parathyroid hormone levels remain unchanged or even decrease, suggesting a shift to right of the parathyroid gland set-point. The reasons for the negative skeletal balance after oophorectomy might be sought therefore at bone tissue level, even if changes in responsiveness and/or of the parathyroid gland set-point could also be contributory.