E. Romagnoli

Skeletal involvement in patients with diabetes mellitus

Studies on skeletal involvement in patients with diabetes mellitus have generated conflicting results, largely because of the pathogenetic complexity of the condition.

Secondary Osteoporosis in Men and Women: Clinical Challenge of an Unresolved Issue

Objective. To evaluate the clinical and etiological factors of osteoporosis. We also tested the FRAX algorithm to compare the assessment of fracture risk in patients with primary or secondary osteoporosis. Methods. A prospective study carried out in a large sample of 123 men and 246 women. All subjects had a biochemical, densitometric, and radiological examination of thoracic and lumbar spine. Results. The prevalence of primary (men 52.9% vs women 50%; p = nonsignificant) and secondary (men 21.1% vs women 17.5%; p = nonsignificant) osteoporosis did not differ between the sexes. In contrast, the prevalence of primary osteoporosis was significantly higher than secondary causes (p < 0.0001) in both men and women. While women came to our attention for prevention of osteoporosis, men sought help because of clinical symptoms or disease-related complications, such as fractures. As evaluated by the FRAX tool, patients with osteopenia do not need treatment, in agreement with Italian guidelines. The estimated risk of major osteoporotic and hip fractures was significantly higher in women with secondary osteoporosis compared to men and also compared to women with primary osteoporosis. Conclusion. The prevalence of secondary osteoporosis in men is similar to that in women and it is less frequent than commonly reported. In patients with secondary osteoporosis, FRAX calculation may provide an estimate of a particularly high fracture risk in patients whose bone fragility is usually attributed to another disease.

Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover.

The most common clinical presentation of primary hyperparathyroidism (PHPT) is nowadays characterized by a slight skeletal involvement. We studied 5 consecutive female patients with PHPT presenting with bone turnover marker levels within the reference range of our Center and whose bone mineral density values were above the usual fracture risk threshold. In each patient we measured, both in basal conditions and daily, for the first 5 days after surgery, the following indexes: serum total (T-ALP) and bone-specific (B-ALP) alkaline phosphatase activity, osteocalcin (BGP, by two different assays), together with the 24-hour urinary excretions of total pyridi-noline (Pyr/Cr) and deoxypyridinoline (D-Pyr/Cr), free deoxypyridinoline (FD-Pyr/Cr), cross-linked N-telopeptide of type I collagen (NTx/Cr), and type I C-telopeptide (CTx/Cr). The markers of both bone formation and resorption significantly decreased after surgery (p<0.001 by multiple ANOVA). Individual post-surgical markers changes were all significant but T-ALP and FD-Pyr, the most pronounced percent reductions being shown by NTx and CTx. The time-course of such variations substantially differed among the various indexes. These results show that bone formation and resorption markers are up-regulated also in PHPT patients with mild skeletal involvement; acute removal of parathyroid hormone excess differently affected the markers of bone turnover in terms of both entity and time-course.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia

OBJECTIVEnTumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D.nnnCLINICAL CASEnHere, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection.nnnCONCLUSIONSnWe report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Massive Tumoral Calcinosis in a Patient on Long‐Term Hemodialysis

A 37-year-old man with end-stage renal disease caused by glomerulonephritis had been undergoing dialysis since 1987. In 1990, he started complaining of pain in both shoulders and in the right hip. A plain radiograph revealed soft tissue calcifications proximate to these three joints. In 1993, owing to unbearable pain with functional limitation, an X-ray was repeated that showed a dramatic lobular periarticular calcification (Fig. 1A, right hip). The patient had been compliant in taking aluminumcontaining phosphate binders and had been treated with oral calcitriol. He came to our attention in 1995 owing to pain, palpable calcifications on both shoulders, and stiffness in the same articulations and in the right hip. He had a slight elevation of calcium-phosphate product (Ca, 10.10 mg/dl;p 5 5.45 mg/dl) and normal values for both 25-hydroxyvitamin D [25(OH)D; 32 ng/ml, normal values (nv), 10 – 40 ng/ml] and 1,25(OH) 2D (25 pg/ml; nv5 16 –58 pg/ml), parathyroid hormone (41.5 pg/ml; nv, 10.6 –54 pg/ml), and isoenzyme of total alkaline phosphatase (16.3 U/liter; normal values (nv), 9.4 –26.2 U/liter). He refused any further radiographic approach except for the measurement of a whole body bone mineral density; this documented the effect of the calcification at the above-mentioned sites (Fig. 1B). The patient, lost at the follow-up, was again contacted at the beginning of 1998; his conditions had worsened so that he was almost unable to move his arms and walking was almost impossible. He agreed to perform a whole body calcium measurement again (Fig. 1C). This documented an increase of global bone mineral content despite a reduction in all the subregions unaffected by the extraskeletal calcification process; this increase was most likely caused by the growing calcinosis masses. The patient was advised to start treatment with sodium thiosulfate based on the few studies available in the literature (1,2) while continuing monitor ing phosphate values with conventional drugs, but unfortunately, he failed to follow this therapy. Even though the pathogenesis of massive periarticular calcifications in dialysis patients is unknown, it is possible that abnormalities of vitamin D metabolism might substantially contribute, as previously suggested by Quarles and coworkers. (3) In fact, our patient also had inappropriately normal values of 1,25(OH) 2D for the degree of renal func tion and hyperphosphatemia. Finally, this report underscores the difficult therapeutic challenge posed by these infrequent manifestations of chronic renal failure.

Measuring serum calcium before and after teriparatide treatment

Dear Editor, We read with interest the excellent paper by Wermers and coworkers [1] specifically designed to assess the impact of teriparatide on serum calcium in patients previously treated with antiresorptive drugs. However, we would like to focus on three points that, in our opinion, deserve further consideration. Firstly, the high prevalence of hypercalcemia (ten patients who failed the screening and nine patients during the antiresorptive phase) seems to suggest a technical problem in measuring serum calcium (rather than an underlying disease). Indeed, this is the case in our current clinical practice. Secondly, the enrollment of patients with hypercalcemia represents a clear violation of the protocol. This has also been considered an important issue in other studies in which, for example, the full-length parathyroid hormone molecule [2] was studied. This should be of particular concern when carrying out investigational studies with this specific drug and in the real world too. In fact, as the authors admit, baseline serum calcium level was significantly correlated with a maximum serum calcium value during teriparatide treatment. Thirdly, the findings of urinary calcium excretion are particularly important from a physiological point of view. It is in fact intriguing that a hormone that should increase the efficiency of calcium reabsorption in the distal nephron [3] determines an increased urinary calcium excretion. This is reminiscent of the paradox of mild primary hyperparathyroidism patients exhibiting hypercalciuria. It could be interesting to know if such an effect, at least initially, is confined to those patients who reach significant elevations of serum calcium (thus substantially increasing the filtered load of calcium) or if it is independent of serum calcium concentration. Finally, we agree with the authors that the clinical significance of mild transient increase in serum and urinary calcium may be deemed of little account also in consideration of the relatively short period of exposure to the hormone.