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Table 1 Recommendations, levels of evidence, grade of recommendation according to the Oxford CEBM and level of agreement in Delphi round*

From: Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children

  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 [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. 4 D 95%
 2 Special attention must be paid to patients with chronic diseases who receive treatments that contribute to osteoporosis development; e.g., GCs, chemotherapy treatments or antiepileptic drugs [17, 19, 20, 23,24,25,26,27,28]. 2b B  
Lifestyle and dietary habits
 3 It is important to identify those children at risk for osteoporosis due to causes related to lifestyle, long-term immobilization or problems of anorexia or malnutrition [19, 29,30,31,32,33,34]. 2a B  
 4 Healthy dietary habits must be established by means of a balanced diet that meets specific calcium and vitamin D requirements for each age and allowing for adequate nutritional intake [35, 36]. 2a B  
 5 Tobacco, caffeine and alcohol use must be avoided in children and adolescents [35, 37, 38] [39,40,41]. 2a B  
 6 High impact and low frequency exercise - e.g., running or jumping - must be recommended for healthy children and adolescents [31, 42,43,44,45,46]. 1a A  
 7 This kind of sport must also be recommended for children with low BMD [23, 47, 48]. 3a C  
 8 It is important to recommend exposure to sunlight on the hands, face and arms between six to eight minutes/day in the summer (avoiding the hottest part of the day between 10 a.m. and 3 p.m.) and 30 min/day during the coldest months of the year [15, 49, 50]. 4 D 90%
Complementary test
 9 Children with chronic diseases are at greater risk of vitamin D deficiency than the general
population. Therefore, it would be advisable to monitor them, mostly during the end of winter [49,50,51].
2a B  
 10 Regarding all children and adolescents who are suspected of suffering from secondary osteoporosis, the following lab work for the initial study is recommended: blood and urine chemistry, urine screening and bone turnover markers (Table 6) [52]. 5 D 83%
 11 The role of bone turnover makers in pediatric populations with bone fragility is insufficiently defined, but they can be useful in treatment follow-up and evaluation. For this reason, they are included in the initial study of these patients [23, 52,53,54,55,56]. 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 Specific complementary tests detailed in Table 7 can be carried out for some children and adolescents depending on the suspected underlying condition [15, 23, 58]. 5 D 90%
 14 Interpretation of analytical values must be done taking into consideration the factors that modify them. These factors are biological (age, sex, pubertal stage, ethnicity) and other controllable variables (circadian rhythm, diet, season of the year) [53, 55,56,57,58,59,60,61]. 2b B  
 15 Since low bone mass has been associated with increased fracture risk, DXA is the most recommended method for pediatric populations in order to assess bone health. However, it does not allow for a prediction of fracture risk [34, 48, 62, 63]. 2a B  
 16 DXA of the lumbar spine and total body less head (TBLH) is the chosen method to measure BMD in pediatric populations, since they are the most accurate and reproducible areas of the skeletal system for this measurement [6, 64, 65]. 2a B  
 17 Data analyses must be carried out using pediatric software (software for adults overestimates BMD) [66, 67]. 2b B  
 18 Vertebrae DXA measurement is recommended for children under the age of five due to its higher reproducibility and shorter time necessary for conducting this test [5, 6, 64, 66, 67]. 2a B  
 19 For children under the age of three, total body BMD is not recommended on a routine basis due to its lack of reproducibility in such young children; rather BMC should be used [5, 6, 64]. 3a C  
 20 Regarding children of short stature (< p3) or with a growth retardation problem, it is recommended to adjust their results by means of a size Z-score [6, 23, 64, 68, 69]. 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 For children with suspected secondary osteoporosis, it is recommended to extend the study with a plain lateral thoracic and lumbar X-ray to assess vertebral compression fractures, particularly if they are receiving GCs [23, 70,71,72,73]. 2b B  
 23 In the event of low bone mass or risk factor persistence, a second plain lateral thoracic and lumbar X-ray should be taken after one year [70, 71] . 3b C  
 24 The minimum time interval to wait before repeating a bone density measurement is six months, a period of one year being advisable, apart from exceptional cases [6, 64, 66, 74, 75]. 3b C  
 25 DXA can be used to assess treatment response after six months in the event of high doses of corticosteroids, chemotherapy, or in situations of malnutrition or active treatment [6, 64, 66, 74]. 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 Oral calcium supplementation could improve BMD in healthy children with a low-calcium diet. Nevertheless, increasing calcium intake by means of calcium-rich foods is preferable to supplementation [36,37,38, 76]. 5 D 90%
 28 With respect to children with chronic diseases, adequate treatment of the disease is the most important step to be taken regarding osteoporosis prevention and treatment [23, 77,78,79]. 2b B  
Treatment
 29 Vitamin D supplementation must be prescribed for all those patients with chronic pathologies presenting levels lower than 20 ng/mL and for those with levels between 20-30 ng/mL who present Z-score ≤ − 2 or any data showing bone fragility [51, 80, 81]. 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 [49,50,51, 82, 83]. 5 D 90%
 32 Treatment with BP should be administered to those pediatric patients with osteoporosis (Z-score ≤ − 2 + pathological fracture or VF regardless of Z-score) [9, 84,85,86,87,88]. 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).
- When patients no longer present active risk factors: patients with Z ≤ -3DS (with a declining trajectory confirmed on at least on two separate occasions with one year apart) [9, 84,85,86,87].
5 D 78%
 34 Intravenous BPs should be used whenever there are VF, if there is some contraindication to the use of oral BPs, or according to the patient’s preferences [88,89,90,91]. 3a B-C  
 35 Oral BPs can be used in the absence of contraindications and VF, or during the de-escalation phase [9, 84,85,86,87]. 5 D 70%
 36 The BP dosage should be discontinued or progressively reduced in those patients not presenting fractures during the preceding year and having reached a Z-score higher than -2 [9, 84,85,86,87]. 5 D 90%
Follow-up
 37 A follow-up is recommended for patients at risk for osteoporosis while other risk factors persist and during treatment with calcium and/or vitamin D3, BPs or other osteoporosis treatments [49, 51, 74]. 4 D 95%
 38 Calcium and phosphorus metabolism (serum levels of calcium, phosphorus, alkaline phosphatase, iPTH and 25-hydroxyvitamin D3) should be evaluated on an annual basis [49, 51]. 4 D 90%
 39 During treatment with vitamin D, it is recommended to monitor serum levels of 25-hydroxyvitamin D3 every 6 to 12 months, unless the dosage is changed. In such cases, patients should be monitored at 3–6 months [49, 51]. 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 [49,50,51, 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 It is recommended to perform simple lateral thoracic and lumbar X-rays to assess VF every 6 months to 2 years (with 1 year being the average), according to the risk factor magnitude and the functional status of the child [51, 71, 74]. 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 During treatment with intravenous BPs, assessments of laboratory parameters are recommended before each administration. For oral BPs, checks every six months are recommended [9, 84,85,86, 88,89,90,91,92]. 5 D 83%
 45 During treatment with BPs, annual DXA is recommended [9, 84,85,86, 88,89,90,91,92]. 5 D 85%
Corticosteroid-induced osteoporosis
 46 Lateral spine x-ray is recommended in order to detect VF at the beginning of treatment
with GCs and after one year [70, 71, 93].
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 For children and adolescents receiving GCs chronically and presenting low BMD (Z-score ≤ − 2) and pathological fractures, it is recommended to use BPs associated with calcium and vitamin D [87, 95, 96]. 1b A  
 51 Lateral spine x-rays or BMD checks with DXA are not recommended on a routine basis for those children and adolescents being treated with inhaled GCs at dosages under 800 mcg/day, unless they present other risk factors [97,98,99]. 1b A  
  1. LE level of evidence, GR grade of recommendation, LADR Level of agreement in Delphi round, GCs glucocorticoids, BMD bone mineral density, BMC bone mineral content, DXA dual-energy x-ray absorptiometry, iPTH intact parathyroid hormone, BPs bisphosphonates, VF vertebral fractures