Background
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Presence of one or more vertebral fractures (VF) in the absence of local disease or high-energy trauma.
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Z-score of bone mineral density (BMD) or bone mineral content (BMC) ≤ − 2 (adjusted for size in cases of children measuring below the 3rd percentile) and a history of clinically significant fractures; specifically:
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two or more long bone fractures occurring by age 10 years; or
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three or more long bone fractures at any age up to age 19 years.
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Methods
Design
Development stages
Results
Recommendation | LE | GR | LADR | |
---|---|---|---|---|
General recommendations | ||||
1 | There is a need to monitor BMD in patients with chronic diseases, especially those of endocrinologic, nutritional, rheumatological, renal, metabolic, hematological, neurological and gastrointestinal origin. There is no universal consensus regarding when and how to carry out such an assessment for all the pathologies involved. Following the existing guidelines for each pathology is therefore recommended [8‐22]. | 4 | D | 95% |
2 | 2b | B | ||
Lifestyle and dietary habits | ||||
3 | 2a | B | ||
4 | 2a | B | ||
5 | 2a | B | ||
6 | 1a | A | ||
7 | 3a | C | ||
8 | 4 | D | 90% | |
Complementary test | ||||
9 | Children with chronic diseases are at greater risk of vitamin D deficiency than the general | 2a | B | |
10 | 5 | D | 83% | |
11 | 5 | D | 80% | |
12 | Measurements of bone turnover makers in urine are not recommended for all patients since the collection of the sample may be not correctly carried out due to the patient’s age or concomitant disease [57]. | 5 | D | 90% |
13 | 5 | D | 90% | |
14 | 2b | B | ||
15 | 2a | B | ||
16 | 2a | B | ||
17 | 2b | B | ||
18 | 2a | B | ||
19 | 3a | C | ||
20 | 2a | B | ||
21 | For children suffering from joint contracture or with mobility problems - e.g., with cerebral palsy - distal femur measurement can be an alternative [68]. | 2a | B | |
22 | 2b | B | ||
23 | 3b | C | ||
24 | 3b | C | ||
25 | 3b | C | ||
26 | In cases of children who initially present normal densitometry results, but in whom risk factor(s) persist, the periodicity of the densitometry must be individualized according to the risk factor associated and an interval of one or two years is advised until peak bone mass is reached [6, 64, 66, 74, 75]. | 5 | D | 95% |
Prevention | ||||
27 | 5 | D | 90% | |
28 | 2b | B | ||
Treatment | ||||
29 | 4 | D | 90% | |
30 | For children and adolescents with a low BMD or osteoporosis, calcium supplementation is recommended, particularly for those patients with a low-calcium diet, as well as supplementation of the proper amount of vitamin D3 in order to keep plasmatic levels of 25-hydroxyvitamin D3 higher than 30 ng/dL [82, 83]. | 2b | B-C | |
31 | The required amount of calcium and vitamin D supply needed in children with pathologies that can jeopardize intestinal absorption or modify their body’s use of these nutrients is unknown. For this reason, in the event that such patients present osteoporosis or low BMD according to chronological age, it is advisable to initially prescribe the dose required to ensure a recommended daily intake of healthy children. Treatment can be modified according to plasmatic 25-hydroxyvitamin D3, iPTH and calciuria levels, which must be monitored every six to twelve months [49‐51, 82, 83]. | 5 | D | 90% |
32 | 1b | A | ||
33 | Treatment with BP can be considered for patients without osteoporosis, but a low BMD in early puberty (Tanner 2): - When active risk factors are present: patients with Z ≤ − 2. 5 SD (with a declining trajectory confirmed at least on two separate occasions with one year apart). | 5 | D | 78% |
34 | 3a | B-C | ||
35 | 5 | D | 70% | |
36 | 5 | D | 90% | |
Follow-up | ||||
37 | 4 | D | 95% | |
38 | 4 | D | 90% | |
39 | 5 | D | 88% | |
40 | During supplementation with calcium and/or vitamin D3, calcium/creatinine levels in urine should be monitored at least once a year. Renal ultrasounds should be conducted to rule out nephrocalcinosis in the event of calciuria increase, or when it is not possible to determine calciuria due to the patient’s age or pathology [49‐51, 82, 83]. | 5 | D | 83% |
41 | DXA is recommended one year after the baseline DXA, and then subsequently every 1 or 2 years depending on the trajectory observed. The minimum interval should be 6–12 months [74]. | 4 | D | 93% |
42 | 5 | D | 73% | |
43 | For pediatric patients with reduced mobility due to cerebral palsy and congenital myopathies, a spine X-ray is recommended at 6–8 years of age, or earlier in the event of back pain, and then periodically until the end of growth [23]. | 5 | D | 88% |
44 | 5 | D | 83% | |
45 | 5 | D | 85% | |
Corticosteroid-induced osteoporosis | ||||
46 | Lateral spine x-ray is recommended in order to detect VF at the beginning of treatment | 2a | B | |
47 | It is recommended to carry out lumbar spine or TBLH DXA within the first six months after the beginning of treatment with GCs, and then every 9 to 12 months if treatment continues [94]. | 4 | D | 85% |
48 | It is recommended to start simultaneous treatment and/ or optimize calcium intake (500–1000 mg/day) and vitamin D 400 IU/day for those patients who are scheduled to receive systemic GCs for three months or more [95]. | 2b | B | |
49 | Treatment with calcium and vitamin D must be maintained for three months after discontinuation of GCs [95]. | 5 | D | 88% |
50 | 1b | A | ||
51 | 1b | A |
Discussion
When osteoporosis should be suspected
Neuromuscular disorders | Cerebral palsy Duchenne muscular dystrophy Rett syndrome Myopathies Diseases resulting in long-term immobilization |
Hematological diseases | Leukemias Hemophilia Thalassemia |
Systemic autoimmune diseases | Juvenile systemic lupus erythematosus Juvenile dermatomyositis Systemic juvenile idiopathic arthritis Systemic sclerosis |
Lung diseases | Cystic fibrosis |
Gastrointestinal diseases | Celiac disease Inflammatory bowel disease Chronic liver disease Cow’s milk protein allergy |
Renal diseases | Nephrotic Syndrome Chronic renal failure |
Psychiatric illnesses | Anorexia nervosa |
Infectious diseases | HIV infection Immunodeficiencies |
Endocrine diseases | Delayed puberty Hypogonadism Turner syndrome Klinefelter Syndrome Growth hormone deficiency Acromegaly Hyperthyroidism Diabetes Hyperprolactinemia Cushing syndrome Adrenal insufficiency Hyperparathyroidism Vitamin D metabolism disorders |
Inborn errors of metabolism | Glycogen storage disease Galactosemia Gaucher disease |
Skin conditions | Epidermolysis bullosa |
Iatrogenesis | Systemic glucocorticoids Cyclosporine Methotrexate Heparin Anticonvulsants Radiation therapy |
Disease / Treatment | BMD assessment |
---|---|
Celiac disease | DXA if: -no adequate dietary adherence -irregular menstruation -anemia -other risk factors for fractures [74] |
Cerebral palsy | Difficult lumbar spine X-ray interpretation in cases of severe scoliosis. Total-body or distal femur DXA (area with higher fracture risk), only if there are fragility fractures [8]. |
Duchenne muscular dystrophy | Baseline DXA and annual monitoring. Lateral spine x-ray: Baseline - On GCs treatment: Repeat every 1–2 years. - Not on GCs treatment: Repeat every 2–3 years. - If back pain or ≥ 0, 5 SD decline in spine BMD Z score on serial measurements over 12-month period: Repeat. Refer to osteoporosis specialist following the first fracture [11]. |
Rett syndrome | Baseline DXA, and serial controls according to individual risk [15]. |
Epilepsy | Consider DXA for epileptic patients receiving anti-epileptic drugs for a prolonged period [13] |
Thalassemia | DXA every 2 years from adolescence [12] |
Inflammatory/ systemic disease | Consider DXA for patients receiving high doses of GCs [74]. |
Juvenile idiopathic arthritis (JIA) | < 6 years: DXA in the presence of fragility fractures. > 6 years: DXA if not presenting rapid remission of JIA or in need of high doses of GCs [18]. |
Neoplasms | Baseline DXA two years after completing chemotherapy with osteotoxic drugs; e.g., MTX, GCs or hematopoietic cells transplantation; or secondary effects that favor osteoporosis development (growth hormone deficiency, hypogonadism, etc.) DXA follow-up based on the results of baseline DXA and persistent risk factors [17] |
Cystic fibrosis | DXA in children ≥ age 8 if: - weight < 90% ideal weight - FEV1 < 50% - Delayed puberty - High dosis of GCs > 90 days per year At 18, all of them [101]. |
Diabetes mellitus | DXA if: - low BMD specific risk factors - increased daily insulin dosis - impaired renal function - fracture history [74] |
Anorexia nervosa | DXA in patients with amenorrhea for more than 6 months [13]. |
Systemic lupus erythematosus | DXA evaluation in patients with prolonged systemic GCs exposure exceeding ≥0.15 mg/kg daily for ≥ 3 months. Repeat on an annual basis if Z-score ≤ − 2 [102]. |
How to prevent osteoporosis
Modifiable | Nutritional | • Caloric intake • Protein intake • Calcium intake • Phosphorus intake • Vitamin D • Others (vitamins K, group B, Mg, K …) |
Lifestyle | • Solar exposure • Physical exercise • Tobacco • Alcohol | |
Partly modifiable | High risk diseases | • Prematurity • Pregnancy and nursing in adolescents • Intestinal malabsorption • Cystic fibrosis • Celiac disease • Inflammatory bowel disease • Food allergies • Chronic lactose intolerance • Chronic liver disease • Chronic kidney disease • Cerebral palsy • Chronic rheumatic diseases … |
Hormonal | • Treatment with glucocorticoids • Hyperparathyroidism • Hypogonadism | |
Non- modifiable | Genetics | |
Sex | ||
Ethnicity |
Age | Calcium (mg) | Vitamin D (IU) |
---|---|---|
0–6 months | 200 | 400 |
6–12 months | 260 | 400 |
1–3 years | 700 | 600 |
4–8 years | 1000 | 600 |
9-18 years | 1300 | 600 |
Diagnosis
Laboratory tests
Laboratory test | Variables to analyze |
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Blood count | |
Blood chemistry | Calcium, ionized calcium, phosphorus, magnesium, total proteins, creatinine, urea, glucose, 25-hydroxyvitamin D3, PTH, TSH, free T4 |
24-hour urine chemistry | Calcium, phosphorus, creatinine, tubular phosphorus reabsorption, sodium |
Urine screening | Ca/Creatininea |
Bone turnover makers | Total alkaline phosphatase |
Studies | |
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1 | Immunoglobulins |
2 | Anti-transglutaminase IgA antibodies |
3 | Cortisol |
4 | Prolactin |
5 | FSH, LH, testosterone |
6 | Homocysteine |
7 | Genetic studies (genes related to osteogenesis imperfecta and disorders characterized by bone fragility) |
Imaging tests
Treatment
Calcium and vitamin D supplementation
Bisphosphonates
Drug | Administration | Dose |
---|---|---|
Pamidronate (2nd generation) | Intravenous (dilute in 100-250 ml physiological saline solution, in 3–4 hours) | < 1 year: 0. 5 mg/kg every 2 months 1–2 years: 0. 25-0. 5 mg/kg/day 3 days every 3 months 2–3 years: 0.375–0.75 mg/kg/day 3 days every 3 months > 3 years: 0. 5–1 mg/kg/day 3 days every 4 months Maximum dose: 60 mg/dose and 11. 5 mg/kg/year |
Neridronate (3rd generation) | Intravenous (dilute in 200–250 ml physiological saline solution, in 3 hours) | 1–2 mg/kg/day every 3–4 months |
Zolendronate (3rd generation) | Intravenous (dilute in 50 ml physiological saline solution, in 30-45 min) | 0.0125–0.05 mg/kg every 6–12 months (maximum dose 4 mg) |
Alendronate (2nd generation) | Oral | 1–2 mg/kg/week < 40 kg: 5 mg/day or 35 mg/week > 40 kg: 10 mg/day or 70 mg/week Maximum dose: 70 mg/week |
Risendronate (3rd generation) | Oral | 15 mg/week (< 40 kg); 30 mg/week (> 40 kg) Maximum dose: 30 mg/week |