High-dose estrogen inhibits bone resorption and stimulates bone formation in the ovariectomized mouse

Abstract Background: Bone degradation in multiple myeloma (MM) is a result of increased bone degradation by osteoclasts that is not compensated for by bone forming osteoblasts. Ideally new drugs used for treatment of MM should target not only the myeloma cells but also the imbalance between bone resorption and bone formation. Statins have been shown to inhibit myeloma cell proliferation and induce apoptosis in vitro. Furthermore statins have been shown to stimulate osteoblasts and inhibit osteoclasts both in vitro and in animal models. Statins are normally used at doses around 20–80 mg/day, but in order to reach serum concentrations that can match the in vitro experiments MM patients were treated with 15 mg/kg/day of Simvastatin (HD-Sim) divided in two daily doses in this study. This high dose has previously been found to be safe for MM patients (Haematologica 2006, 91,542–545) Patients and methods: Six patients with advanced MM have been included in this pilot study, 4 males and 2 females with an average age of 68 years and an average duration of disease of 43 months. The patients were treated with 2 cycles of HD-Sim for seven days followed by a break of 21 days in a 4-weeks cycle. Two of the patients were treated with bisphosphonates during the study, and 4 had previously been treated with bisphosphonates. Endpoints are change in concentrations of markers of osteoclast activity (TRAP) or bone resorption (CTX, NTX, ICTP) or markers of bone formation (Osteocalcin and PINP). Cholesterol, OPG and DDK-1 were also measured. Results: Two patients completed the protocol with two cycles of HD-Sim at full dose, 2 patients were reduced to 7.5 mg/kg/day simvastatin in cycle 2 due to nausea and diarrhea and 2 patients left the protocol after 3 weeks (deaths not related to high dose simvastatin). All patients experienced gastrointestinal toxicity grade 1–2. Myalgia and other muscular symptoms grade 1–2 were reported by 5 patients but were not associated with an increase in creatin kinase. TRAP and NTX activity in serum increased for all 6 patients during the seven days of treatment with HD-Sim indicating that bone resorption may have been stimulated rather than inhibited. The other markers of bone resorption and the bone formation markers showed no change. All patients responded with a significantly reduced level of cholesterol in serum. None of the patients showed any reduction in free monoclonal light chains or monoclonal proteins in serum during treatment with HD-Sim and 2 of the 4 patients completing the protocol showed progression of diseases. Conclusion: This pilot study of HD-Sim in advanced MM has been terminated due to lack of response and evidence from two markers of osteoclast activity (TRAP) and bone resorption (NTX) that HD-Sim may be harmful rather than beneficial in MM.

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Bortezomib-Thalidomide-Dexamethasone as Primary Induction Therapy for Newly Diagnosed Multiple Myeloma Significantly Decreases Bone Resorption While Sparing Bone Formation as Compared to Thalidomide-Dexamethasone

Blood ◽

10.1182/blood.v112.11.5117.5117 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5117-5117 ◽

Cited By ~ 1

Author(s):

Patrizia Tosi ◽

Elena Zamagni ◽

Paola Tacchetti ◽

Giulia Perrone ◽

Michela Ceccolini ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Bone Resorption ◽

Bone Formation ◽

Induction Therapy ◽

Phase Iii ◽

High Dose ◽

Newly Diagnosed ◽

Bone Formation Markers

Abstract Bone disease occurs in approximately 80% of patients with newly diagnosed multiple myeloma (MM) and is caused by the interaction of the neoplastic clone with bone marrow microenvironment, ultimately resulting in an altered balance between bone resorption and bone formation. It has been previously reported that therapies aimed at eradicating the myeloma clone could contribute to decrease bone resorption, even though bone formation remains impaired even in responding patients, due to the use of high-dose steroids. It has been recently demonstrated, both in vitro and in animal models, that Bortezomib improves bone formation by stimulating osteoblasts. In order to test whether this activity was retained also in vivo, we evaluated markers of bone resorption (serum crosslaps) and bone formation (serum osteocalcin-OC and bone alkaline phosphatase - BAP) in a series of patients who were enrolled in the “Bologna 2005” phase III clinical trial at our Center. By study design, after registration patients were randomized to receive three 21-days courses of induction therapy with either VTD (Bortezomib, 1.3 mg/sqm on d 1, 4, 8, and 11, plus Dexamethasone, 40 mg on each day of and after Bortezomib administration plus Thalidomide 200 mg/d from d 1 to 63.) or TD (Thalidomide as in VTD and Dexamethasone 40 mg/d on d 1–4 and 9–12 of every 21-d cycle), prior to stem cell collection and double autologous stem cell transplantation. As of January 2008, 27 patients (19 male and 8 female, median age = 57.5 yrs) entered the sub-study; of these, 15 and 12 patients were randomized in the VTD and TD arm, respectively. At diagnosis, both groups of patients showed a marked increase in serum crosslaps as compared to upper baseline limit (7321±1445pmol/L in the VTD arm and 11140±2576pmol/L in the TD arm) while both OC and BAP were reduced as compared to lower baseline limits. After completion of the induction therapy, serum crosslaps were significantly decreased in both treatment groups (2747±319pmol/L in VTD arm, p=0.007; 3686±1084pmol/L in the TD arm, p=0.0015). In the TD group a significant further reduction in bone formation markers was also observed (42% reduction in serum OC and 30% in BAP, p=0.03 and 0.04 as compared to pre-treatment values); on the contrary, in the VTD arm both OC and BAP were not significantly decreased as compared to baseline values (15% and 11% for OC and BAP, respectively). These data suggest that incorporation of Bortezomib into induction therapy counteracts the inhibitory effects of high-dose steroids on osteoblastogenesis, thus sparing bone formation.

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Lung Transplantation in a Patient With Osteogenesis Imperfecta and Osteoporosis

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.417 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A205-A205

Author(s):

Lena Fan ◽

Luke J Benvenuto ◽

Margaret Nolan ◽

Angela DiMango ◽

Elizabeth Shane ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Osteogenesis Imperfecta ◽

Lung Transplantation ◽

Urinary Calcium ◽

Multiple Drug ◽

High Dose ◽

Full Time ◽

Restrictive Lung Disease

Abstract Background: Osteogenesis imperfecta (OI) and transplantation (TP) are independently associated with fractures. Yet reports regarding the skeletal effects of organ TP in OI are limited. We report the early skeletal outcomes in an OI patient with osteoporosis who underwent lung TP. Clinical Case: A 35-year-old man with moderate/severe OI and severe bronchiectasis was admitted for progressive respiratory failure and expedited lung TP evaluation. OI was diagnosed at age 10 after sustaining a hairline coccyx fracture when falling off a stool; scoliosis was diagnosed at age 14; additional fractures included ankle (18 y), toes (28 y) and rib (34 y). He had dentogenesis imperfecta, but no hearing loss, easy bruising or OI family history. Bronchiectasis also began at age 10 and progressed, with multiple drug resistant infections and glucocorticoid (GC) treatments. At admission, he was on 6L oxygen and bed-bound from dyspnea. Notably, he had been rejected twice for TP because of his bone disease. Admission medications included calcium, D3, famotidine, inhaled fluticasone, tobramycin, and tiotropium bromide. His exam was notable for height 5’5”, BMI 16.5 kg/m2, kyphoscoliosis, blue sclera and joint laxity. Labs were notable for (mg/dl): serum calcium 9.4, magnesium 2.4, phosphate 4.4; albumin 4.2 g/dl, alkaline phosphatase 75 U/L, 25(OH)D 34 ng/ml, sCTX 535 pg/ml, urinary calcium 370 mg/24 hr. DXA showed T-scores of -4.7 (lumbar spine), -3.3 (femoral neck), -3.2 (total hip), -2.6 (1/3 radius). Endocrinology was consulted about the skeletal risk of lung transplantation. Discussion and Follow-up:The patient’s manifestations of OI increased the risk of adverse skeletal outcomes. His high CTX suggested increased bone resorption, often seen with OI; bone formation was not directly measured but in OI is frequently reduced. Notably, his bronchiectasis was likely related to the OI: in addition to restrictive lung disease in OI, the abnormal type 1 collagen likely alters alveolar structure and elasticity. His risk for post-TP fractures was high given that the expected post-TP bone loss would likely be exacerbated by high dose GCs further increasing bone resorption and reducing presumed low bone formation. Nevertheless, because he had never sustained a major fracture even without OI treatment, the decision was made to proceed. He received zoledronate (ZOL) 5 mg IV and underwent an uncomplicated double lung transplant; initial high dose GCs were tapered to prednisone 10 mg/d. Three months later, he has steadily rising lung function, excellent functional status, and is working full time. A current sCTX of 73 pg/ml suggests that bone loss is not increased. Admittedly, the patient remains within the early high-risk fracture window. Yet this case is the first report to our knowledge which suggests that lung TP in an OI patient treated with ZOL did not lead to fracture in the early post-TP period.

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Consolidation Therapy with Bortezomib, Thalidomide and Dexamethasone (VTD) Regimen After ASCT in Myeloma Patients Who Do Not Receive Bisphosphonates Reduces Bone Resorption and RANKL/OPG Ratio but Seems to Have No Effect On Bone Formation and Angiogenesis.

Blood ◽

10.1182/blood.v114.22.3863.3863 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3863-3863 ◽

Cited By ~ 1

Author(s):

Evangelos Terpos ◽

Dimitrios Christoulas ◽

Magdalini Migkou ◽

Maria Gavriatopoulou ◽

Athanasios Papatheodorou ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Metabolism ◽

Serum Levels ◽

High Dose ◽

Osteoblastic Activity ◽

Bone Specific Alkaline Phosphatase ◽

Bone Formation Markers ◽

Tracp 5B ◽

Angiogenic Cytokines

Abstract Abstract 3863 Poster Board III-799 Bortezomib (V) monotherapy is associated with increased osteoblastic activity, reduced osteoclast function and decreased angiogenesis in relapsed/refractory myeloma (MM). The co-administration of zoledronic acid in all reported studies to-date may suggest a synergistic stimulation on osteoclast/osteoblast interactions by the two agents but has not allowed the independent evaluation of V on bone metabolism. Furthermore, the combination of V with other agents, such as thalidomide (T), melphalan (M) and dexamethasone (D), although it reduced osteoclast activity, it did not enhance osteoblast function. We evaluated the effect of VTD consolidation on bone metabolism and angiogenesis in MM patients who underwent high-dose M followed by ASCT. In this prospective study, only patients in first remission or with primary refractory disease to one frontline treatment were included. Patients did not receive any bisphosphonate during or post-ASCT as well as throughout the period of VTD consolidation. VTD started on day 100 after ASCT: V was administered at a dose of 1.0 mg/m2 on days 1,4,8,11; T was given at a dose of 100 mg/day, po, on days 1-21 and D at a dose of 40 mg/day on days 1–4 of a 21-day cycle. Patients received 4 cycles of VTD (first block), were followed without treatment for 100 days and then received another 4 cycles of VTD (2nd block). Patients were assessed for skeletal-related events (SREs) throughout the period of the study (12 months). Bone remodeling was studied by the measurement of the following serum indices before and after each block of VTD (4 measurements for each patient): i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)], ii) osteoblast inhibitor dickkopf-1 (Dkk-1), iii) bone resorption markers (CTX and TRACP-5b) and iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin (OC)]. Angiogenic cytokines such as VEGF, angiogenin (ANG), angiopoietin (Angp)-1 and -2, and bFGF were also studied on the same dates. So far, 32 patients have completed the first block of VTD, while 16 patients have completed both VTD blocks. Just before VDT administration, 10 patients were in CR (4 in sCR), 14 in vgPR and 8 in PR. Although most of these patients were rated as vgPR or better, they had increased serum levels of sRANKL (p=0.037), Dkk-1 (p=0.001), CTX (p=0.002), TRACP-5b (p<0.001), VEGF (p<0.001), bFGF (p<0.001), ANG (p=0.006) and reduced levels of Angp-1/Angp-2 ratio (p<0.001) compared to 18 healthy controls of similar age and gender, indicating sustained osteoclast and angiogenic activity despite minimal tumor load. Levels of sRANKL and Dkk-1 positively correlated with resorption markers (p<0.01). The first block of VTD resulted in a significant reduction of sRANKL (p=0.001), sRANKL/OPG (p=0.005), CTX (p=0.001), TRACP-5b (p=0.032), but also of bALP (p=0.022) and OC (p=0.02), while Dkk-1 and the majority of angiogenic cytokines showed no alterations (only Angp-1/Angp-2 ratio had a borderline increase, p=0.044). After the first block of VTD, 39% of patients improved their status of response; however alterations of the studied molecules were irrespective of further response or not improvement. Before the administration of the 2nd block of VTD, RANKL, RANKL/OPG and CTX were reduced compared to values after the first block of VTD (p=0.01, p=0.027 and p=0.005, respectively). These parameters were further reduced after the completion of the study (p<0.05). On the contrary, Dkk-1 was increased between the end of the first block of VTD and the initiation of the 2nd (p=0.008) but was reduced after the 2nd block of VTD (p=0.037). OC had no further alterations, while bALP was increased before the 2nd block of VTD (p=0.012) and showed no changes thereafter. VEGF, ANG, and Angp-1/Angp-2 were increased during the resting period between the two VTD blocks and remained unchanged thereafter. During the study period, only one patient developed a SRE (i.e. radiation to bone). As of July 2009, 8 of 32 patients have developed progressive disease. The median TTP after ASCT was 27 months (CI 95% 16.3-37.6). The results of this ongoing study suggest that VTD consolidation post-ASCT, without the presence of bisphosphonates, reduces RANKL and bone resorption and is associated with a very low incidence of SREs. However, bortezomib was not able to produce a significant anabolic effect on bones when combined with TD even in these patients with low myeloma burden, while its effect on angiogenic cytokines was modest. Disclosures: Terpos: Janssen-Cilag: Consultancy, Honoraria. Dimopoulos:Janssen-Cilag: Honoraria; Celgene: Honoraria.

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Immediate Fall of Bone Formation and Transient Increase of Bone Resorption in the Course of High-Dose, Short-Term Glucocorticoid Therapy in Young Patients with Multiple Sclerosis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-0164 ◽

2004 ◽

Vol 89 (10) ◽

pp. 4923-4928 ◽

Cited By ~ 91

Author(s):

Andrea Dovio ◽

Laura Perazzolo ◽

Giangiacomo Osella ◽

Massimo Ventura ◽

Angela Termine ◽

...

Keyword(s):

Multiple Sclerosis ◽

Bone Resorption ◽

Bone Formation ◽

Young Patients ◽

Transient Increase ◽

Glucocorticoid Therapy ◽

High Dose ◽

Short Term

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The Addition of Bortezomib to the Combination of Lenalidomide and Dexamethasone Increases Bone Formation in Relapsed/Refractory Myeloma: a Prospective Study in 91 Patients.

Blood ◽

10.1182/blood.v114.22.1815.1815 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1815-1815 ◽

Cited By ~ 3

Author(s):

Evangelos Terpos ◽

Dimitrios Christoulas ◽

Efstathios Kastritis ◽

Maria Roussou ◽

Maria Gavriatopoulou ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Prospective Study ◽

Bone Remodeling ◽

High Dose ◽

Type I ◽

Percentage Increase ◽

Bone Resorption Markers ◽

Median Increase ◽

A Prospective Study

Abstract Abstract 1815 Poster Board I-841 Bortezomib is the first-in-class proteasome inhibitor with established activity in multiple myeloma (MM), which also increases osteoblast function both in vitro and in vivo. The addition of bortezomib to the combination of lenalidomide and dexamethasone (RD) regimen seems to increase the RD efficacy. There are very limited data in the literature for the effect of RD on bone metabolism while there are no reports for the effect of BRD on myeloma bone disease. The aim of this study was to evaluate the effect of BRD and RD on bone remodeling of patients with relapsed/refractory MM. We studied 91 patients who participated in a prospective study in which patients with pre-existing peripheral neuropathy (PN) grade <2 received BRD, while patients with PN of grade 2 or more received RD, regardless of their performance status and renal function. In BRD arm, patients received bortezomib at a dose of 1 mg/m2 on days 1, 4, 8 and 11; lenalidomide 15 mg on days 1-14 (or at a lower dose if creatinine clearance (CrCl) was <30 ml/min) and dexamethasone 40 mg, PO, on days 1-4, in a 21-day cycle. In RD arm, patients received lenalidomide on days 1-21 at a dose based on their CrCl, according to guidelines, and dexamethasone 40 mg, PO, on days 1-4 and 15-18 for the first 4 cycles and only on days 1-4 thereafter, every 28 days. All patients also received 4 mg zoledronic acid, iv, monthly. Bone remodeling was studied by the measurement of a series of serum indices, on day 1 of cycles 1, 4 & 7, in patients and in 31 healthy controls of similar age and gender: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)], ii) osteoblast inhibitor dickkopf-1 (Dkk-1), iii) bone resorption markers [C-telopeptide of collagen type-I (CTX) and 5b-isoenzyme of tartrate resistant acid phosphatase (TRACP-5b)], and iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin (OC)]. Radiological skeletal survey was performed at baseline, after 6 cycles of therapy and then as needed, while patients were assessed for skeletal-related events (SREs) throughout the period of the study. As of July 2009, 80 patients (43M/37F, median age 67 years) have received 6 cycles of therapy (40 in each treatment arm) and the bone markers measurements have been completed and analyzed. Myeloma patients at baseline had increased serum levels of Dkk-1 (p<0.001), sRANKL (p=0.006), and bone resorption markers (p<0.01) compared to control group. On the contrary, both markers of bone formation were significantly reduced compared to controls (p<0.001). Strong correlation was observed between Dkk-1 and sRANKL/OPG ratio (r=0.639, p<0.001). Objective response was 60% (24/40 patients) in RD and 62.5% (25/40 patients) in BRD. BRD administration resulted in a significant reduction of Dkk-1 (p=0.031) and increase of OC (p=0.002) after 3 cycles of therapy which was continued after 6 cycles of therapy. Furthermore, BRD led to a reduction of sRANKL (p=0.023) and sRANKL/OPG ratio (p=0.027) and a significant increase of bALP (p=0.01) after 6 cycles of treatment. These changes were irrespective of treatment response. In BRD patients, percentage reduction of Dkk-1 strongly correlated with percentage increase of bALP after 6 cycles of therapy (r=-0.682, p=0.004). In patients who received RD no significant alterations in markers of bone remodeling were observed. However, patients who responded to RD showed a reduction in CTX (p=0.039) compared with those who did not respond after 6 cycles of therapy. Patients who received 6 cycles of RD showed an increase of Dkk-1 levels: responders had a median increase of 9% while non-responders had a median increase of 91% compared to baseline values (p<0.01). The percentage change of sRANKL (p=0.007) and Dkk-1 (p=0.009) was significantly different between patients who received BRD and those who received RD: both molecules were reduced after 6 cycles of BRD while both were increased after six cycles of RD. No SREs were observed in the BRD arm while two patients treated with RD who had not responded to therapy developed a vertebral pathological fracture. Our study suggests that RD regimen does not seem to have any effect on bone formation even in responding patients with relapsed/refractory MM, possibly due to the presence of high dose dexamethasone and to the enhancement of Dkk-1 expression by lenalidomide. On the contrary, patients who received BRD had an increased bone formation, at least partially due to a significant reduction of Dkk-1, reflecting the strong anabolic effect of bortezomib in MM patients. Disclosures Terpos: Janssen-Cilag: Consultancy, Honoraria.

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Effects of Vitamin E on Bone Biomechanical and Histomorphometric Parameters in Ovariectomized Rats

Journal of Osteoporosis ◽

10.1155/2013/825985 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

Rafaela G. Feresin ◽

Sarah A. Johnson ◽

Marcus L. Elam ◽

Jeong-Su Kim ◽

Dania A. Khalil ◽

...

Keyword(s):

Vitamin E ◽

Bone Resorption ◽

Bone Formation ◽

Trabecular Bone ◽

Bone Structure ◽

Lumbar Vertebrae ◽

Lumbar Vertebra ◽

Ovariectomized Rats ◽

Control Group ◽

High Dose

The present study examined the dose-dependent effect of vitamin E in reversing bone loss in ovariectomized (Ovx) rats. Sprague-Dawley rats were either Sham-operated (Sham) or Ovx and fed control diet for 120 days to lose bone. Subsequently, rats were divided into 5 groups (n=12/group): Sham, Ovx-control, low dose (Ovx + 300 mg/kg diet; LD), medium dose (Ovx + 525 mg/kg diet; MD), and high dose (Ovx + 750 mg/kg diet; HD) of vitamin E and sacrificed after 100 days. Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase compared to the Ovx-control group. Bone histomorphometry analysis indicated a decrease in bone resorption as well as increased bone formation and mineralization in the Ovx groups supplemented with MD and HD of vitamin E. Microcomputed tomography findings indicated no effects of vitamin E on trabecular bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced fourth lumbar vertebra quality as evidenced by improved ultimate and yield load and stress when compared to Ovx-control group. These findings demonstrate that vitamin E improves bone quality, attenuates bone resorption, and enhances the rate of bone formation while being unable to restore bone density and trabecular bone structure.

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Bone Involvement in Multiple Myeloma Patients Carrying the T (4;14) Chromosomal Translocation.

Blood ◽

10.1182/blood.v108.11.4996.4996 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4996-4996

Author(s):

Patrizia Tosi ◽

Carolina Terragna ◽

Testoni Nicoletta ◽

Elena Zamagni ◽

Matteo Renzulli ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Resorption ◽

Bone Formation ◽

Chromosomal Abnormality ◽

Surrogate Marker ◽

Chromosomal Translocation ◽

Bone Involvement ◽

Disease Stage ◽

High Dose ◽

Spine Mri

Abstract Chromosomal translocations involving the immunoglobulin heavy chain switch region (IgH) are quite common in multiple myeloma (MM), and some of them can reliably predict disease outcome. In particular, t(4;14) chromosomal abnormality is one of the most adverse prognostic factors for response duration and survival after high dose therapy and autologous stem cell transplantation. Despite the dismal prognosis, however, in this subset of patients, bone involvement, as evaluated by spine MRI, is relatively infrequent, at variance to what has been observed in other MM subtypes according to TC classification. In the present study we aimed at further testing this hypothesis by analyzing the extent of whole bone involvement in patients showing t(4;14) chromosomal translocation as compared to negative patients. For this purpose, 50 newly diagnosed MM patients (32M, 18F, median age = 54 yrs) underwent evaluation of total skeletal X-ray, whole spine MRI and, at the same time, quantification of markers of bone resorption (urinary NTX, PYR and DPYR and serum crosslaps) and bone formation (bone alkaline phosphatase-BAP and osteocalcin) was performed. Using a real-time PCR assay to detect the presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), we found 15 patients carrying this chromosomal abnormality, 7 of whom (46%) were also positive for the deletion of chromosome 13, this abnormality was detected in 11/35 (31%) patients who proved negative for IgH/MMSET hybrid transcript. The two groups of patients did not differ significantly in terms of median age, distribution of M protein isotype and light chain, beta-2 microglobulin, bone marrow plasma cell infiltration and disease stage. Spinal MRI was negative in 3/15 (20%) t(4;14) positive patients as compared to 12% t(4;14) negative patients; skeletal involvement, however, was more pronounced in t(4;14) positive patients (median skeletal score = 6.24, as compared to 3.58 in t(4;14) negative cases, p= 0.00). These data were confirmed by the evaluation of bone resorption markers; specifically, serum crosslaps were significantly increased in patients with t(4;14) abnormality compared to negative individuals (7984 pmol/L±1682SE vs 5123pmol/L±783SE p=0.04). Conversely, no difference in bone formation markers was found in the two groups of patients. Our results indicate that, despite a spinal involvement at MRI that is comparable to what is observed in negative patients, individuals who are t(4;14) positive show a more pronounced bone resorption pattern, this in contrast to what has been reported so far, but in line with the aggressive features of the disease in these patients.

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[18F]Fluoride PET Indicates Reduced Bone Formation in Severe Glucocorticoid-induced Osteoporosis

Nuklearmedizin ◽

10.1055/s-0038-1629797 ◽

1998 ◽

Vol 37 (02) ◽

pp. 76-79 ◽

Cited By ~ 8

Author(s):

T. D. Kirchhoff ◽

W. Burchert ◽

J. v. d. Hoff ◽

H. Zeidler ◽

H. Hundeshagen ◽

...

Keyword(s):

Bone Formation ◽

Multiple Organ ◽

High Dose ◽

Multiple Fractures ◽

Glucocorticoid Treatment ◽

Organ Manifestations ◽

Diagnostic Benefit ◽

Sharp Syndrome ◽

18F Fluoride

SummaryA 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

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