Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study

2021 ◽  
Vol 34 (4) ◽  
pp. 441-447
Author(s):  
Ismail Solmaz ◽  
Mehmet Akif Ozdemir ◽  
Ekrem Unal ◽  
Ummuhan Abdurrezzak ◽  
Sebahattin Muhtaroglu ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Mineral ◽  
Vitamin D3 ◽  
Lymphoblastic Leukemia ◽  
Vitamin K2 ◽  
Control Group ◽  
Study Group ◽  
Mineral Density

Abstract Objectives Current treatment protocols in acute lymphoblastic leukemia (ALL) are associated with high remission rates and long life expectancy, enhancing the importance of quality of life and prevention of treatment-related complications in patient care. As osteoporosis is a frequent complication in patients under chemotherapy, we investigated the effect of vitamin K2 (100 mcg menaquinone-7) and vitamin D3 (10 mcg calcitriol) on bone metabolism in children with ALL. Methods Twenty-nine consecutive patients recently diagnosed with B precursor ALL (B-ALL) and treated according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Münster 2000 protocol were randomly assigned into study and control groups. The study group (n=15, M/F: 8/7, age 1–14.5 years, mean 6.5 years) received vitamin K2 and vitamin D3 with their chemotherapy, while the control group (n=14, M/F 9/5, age 2–17 years, mean 7.1 years) received chemotherapy only. Serum calcium, phosphorus, magnesium, alkaline phosphatase, bone-specific alkaline phosphatase, uncarboxylated osteocalcin (ucOC), tartrate resistant acid phosphatase 5b, carboxyl terminal procollagen propeptide (PICP), osteoprotegerin (OPG), and receptor activator nuclear kappa B ligand (RANKL) were measured and bone mineral density (BMD) was determined at baseline and first, second, third and sixth months. Results The study group had higher serum OPG/RANKL ratio and lower ucOC levels compared to the control group at the first month; PICP levels were higher in the study group at second and third months. Conclusions These results suggest an early beneficial effect of the combination of vitamin K2 and vitamin D3 on BMD in ALL patients especially during the period of intensive steroid therapy in the first months.

Bone Mineral Density, Fracture Risk and Avascular Bone Necrosis in Childhood Acute Lymphoblastic Leukemia; an Up-Date of the Prospective DUTCH ALL9 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1962-1962
Author(s):  
Marry M. Van den Heuvel-Eibrink ◽  
Inge M. Van der Sluis ◽  
Bert A. Leeuw ◽  
Gaby Kardos ◽  
Lizet M. te Winkel ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Fracture Incidence ◽  
Rapid Decline ◽  
Mineral Density ◽  
Discontinuation Of Treatment ◽  
One Year

Abstract The high cumulative dose of dexamethasone, applied in the DCOG ALL9 protocol, prompted us to investigate the risk of osteoporosis, fractures and avascular necroses of bone (AVN) in children treated with acute lymphoblastic leukemia (ALL). Fracture risk and incidence of symptomatic AVN was assessed in 778 patients(482 boys, 297 girls), included in the ALL9 protocol since 1997. Total cumulative doses (TCD) of dexamethasone were 1370 mg/m2 and 1244 mg/m2 and of MTX 8.1g/m2 13.6g/m2 for NHR and HR patients respectively. No CNS-irradiation was applied. In children aged >3 years, lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXAscan), at diagnosis(T0), after 32 weeks(T1), at discontinuation of treatment at 109 weeks(T2), and one year after discontinuation of treatment(T3). Results were expressed as standard deviation scores (SDS). Symptomatic AVN was defined as on MRI confirmed AVN lesions in combination with non-vincristine related persistent pain in arms or legs. Fractures were reported in 82/778 (10.5%) patients. Most occurred after mild trauma. No difference was found in fracture incidence between boys and girls. BMD was measured in 387/427 (90.6%) eligible patients. Median BMD-SDS was significantly lower than zero at all times of evaluation, the lowest BMD values were found at T2 (−1.47 SDS). Fracture risk was 3.9 times higher as compared to healthy school children. Fracture incidence was correlated with BMD at T2 and T3(p=0.04 and p=0,04 respectively), but not at T0 and T1. A significant more rapid decline in BMD from T0 to T2 and to T3 was seen in patients with fractures as compared to patients without fractures. After discontinuation of therapy, BMD recovered faster in cases without fractures. Symptomatic AVN occurred in 33/778 (4.2%) of our patients (med age 14, range 6,5–18 years) showing irreversibility in 22 % of the cases. Differences found in the incidence between the centers may suggest underestimation of the risk of fractures and AVN in this prospective study. Children with ALL show a significantly increased fracture risk. Patients with a more severe reduction in BMD during treatment are more susceptible to fractures. The AVN incidence in this protocol did not exceed previous reports of prednisolone-based protocols.

Aggravated Bone Density Decline after Symptomatic Osteonecrosis in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2260-2260
Author(s):  
Marissa den Hoed ◽  
S.M.F. Pluijm ◽  
Mariël L. Te Winkel ◽  
Hester A. de Groot-Kruseman ◽  
Marta Fiocco ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Bone Mineral ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Bone Destruction ◽  
Mineral Density ◽  
Pediatric All ◽  
Cessation Of Treatment

Abstract Background: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side effects can influence each other’s development during pediatric ALL treatment. Methods: BMD and the incidence of symptomatic ON were prospectively assessed in 466 patients with ALL (4-18 years of age) treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Symptomatic ON was defined as persistent pain in arms or legs not caused by vincristine administration, and confirmed by magnetic resonance imaging. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) were measured by dual X-ray absorptiometry at ALL diagnosis, after 32 weeks of treatment, at cessation of treatment (109 weeks) and 1 year after cessation of treatment. BMD was expressed as age-matched and gender-matched standard deviation scores (SDS; Z-score). Multivariate linear mixed models were adjusted for age at diagnosis. Results: Thirty patients (6.4%) suffered from ON. At cessation of treatment, mean BMDLS was -1.28 SDS (SD: 1.27, n=332; p<0.01) and BMDTB was -0.74 SDS (SD: 1.29, n=65; p<0.01) lower in ALL patients compared to their healthy peers. At baseline, BMDLS and BMDTB did not differ between patients who developed or who did not develop ON (mean BMDLS ON+: -0.90 vs. ON-: -1.14, p=0.36; mean BMDTB ON+: 0.07 vs. ON-: 0.25 p=0.65). At cessation of treatment, patients with ON seem to have a trend for a lower mean BMDLS (ON+: -1.68 vs. ON-: -1.31, p=0.18) and they have a lower mean BMDTB (ON+: -1.91 vs. ON-: -0.59, p=0.01) than patients without ON. Multivariate analyses showed that BMDTB change during follow-up was significantly different for patients with ON than without ON (interaction group time, p=0.04). Between BMD measurements before and after the diagnosis, patients with ON seemed to have a more rapid decline of BMDTB than in patients of the same age without ON (mean BMDTB difference -1.13 vs. -0.62, p=0.10). Conclusion: We conclude that symptomatic ON and low BMD during antileukemic treatment co-occur in pediatric ALL patients. BMD status at ALL diagnosis does not seem to precede ON. However, the development of ON seems to aggravate BMD decline during antileukemic treatment, most likely due to bone destruction and the advised physical immobilization. Disclosures No relevant conflicts of interest to declare.

Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia

2002 ◽  
Vol 141 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Inge M. van der Sluis ◽  
Marry M. van den Heuvel-Eibrink ◽  
Karel Hählen ◽  
Eric P. Krenning ◽  
Sabine M.P.F. de Muinck Keizer-Schrama
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Acute Lymphoblastic Leukemia ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Mineral Density
Sign in / Sign up

Export Citation Format

Share Document