This is the largest case series of vitamin D deficient rickets reported to date from a developed country. Recently immigrated infants or first generation offspring of immigrant parents, with maternal vitamin D deficiency and exclusive or prolonged breast feeding were prominent in this series, and males were more commonly affected. The observed increase mirrors immigration trends, and while increased awareness of vitamin D deficiency and rickets/osteomalacia in Australia in recent years6,9,10,11
may have contributed to increase case detection, it is of concern that severe infantile and childhood6,11
manifestations have continued.
Immigration trends over the last decade have shown a demographic shift in region of origin, with a major increase from North African, Middle Eastern, and Asian countries.12
Over the last two years of the study period, North African and Middle Eastern immigration rose by 76%, the largest increase of any ethnic group. The number of African children presenting, predominantly North African, rose from four cases in each of 2001 and 2002 (25% and 30% of total cases respectively), to 22 cases in 2003 (62% of total cases). The prevalence of rickets and vitamin D deficiency in adult women in these regions is well reported.5,13,14
Furthermore, 74% of pregnant women from the Horn of Africa had 25‐hydroxyvitamin D levels <25 nmol/l, in a study from Melbourne.15
These high maternal risk factors persist, even though the majority of our cohort (79%) were born in Australia. Vitamin D levels are not performed as part of the screening process for immigrants arriving in Australia and data do not exist on the effect of residing in Australia on maternal vitamin D levels after immigration. It is likely that vitamin D levels drop further in immigrant women after arriving in Australia, with less time spent outdoors.16
Research has shown that 25‐hydroxyvitamin D levels of 50 nmol/l are required to prevent secondary hyperparathyroidism,17
while the level for optimal skeletal health may be as high as 80 nmol/l.18
Many commercial assays currently show lower normal reference ranges considerably below this. Reduced sunlight exposure is an important factor in the aetiology of vitamin D deficiency, as intake from dietary sources, such as oily fish, eggs, and butter/margarine,19
account for only 10% of the daily requirement.20
Human milk supplies less than 100 IU vitamin D/day in vitamin D sufficient mothers.21,22,23
Sydney has an annual daily average of 6.95 hours of sunlight, with 6.58 hours per day in winter,24
easily adequate for the recommended 30 minutes per week, wearing only a nappy, or 2 hours a week fully clothed without a hat, in infants.23
The swaddling of babies, poor accommodation, ethnic and religious practices, and campaigns to decrease sunlight exposure may all increase the risk of rickets.25
Ultraviolet (UV) radiation is 12–15% higher in Australia compared to similar locations in the northern hemisphere,26
with skin cancer rates among the highest in the world. UV light does not penetrate clothing or glass and sunscreen affects vitamin D status. Sunscreen with a UV protection factor of 8 reduces the skin's ability to produce vitamin D by 97.5%17
and 15+ sunscreens are commonly used in Australia. Darkly pigmented individuals are further compromised with melanin competing with 7‐dehydrocholesterol in the skin for UV‐B photons, resulting in a highly increased requirement for sun exposure to achieve the same vitamin D levels.27
Differences have been shown between light and dark skinned individuals in milk cholecalciferol, ergocalciferol, and 25‐hydroxyvitamin D levels.22
Almost two thirds of cases in the present study were male, who presented earlier and more acutely than females. A male predominance has been shown in previous retrospective studies, in Australia, Ethiopia, and the USA,6,14,28,29
but not uniformly, with a Copenhagen based study showing a large female predominance.30
The reasons for the male predominance are unclear and immigration gender ratios do not account for this.12
Significantly more males were breast fed and exclusively breast fed, and this may reflect preferential treatment given to male children, which is recognised in some cultures. Vitamin D deficiency negatively affects growth and is a recognised cause of failure to thrive. Children affected by rickets are smaller, both in height and weight, than the normal population.7
In this cohort, males had a significantly lower weight z score, compared to females, which has not been reported previously.
The increasing frequency of rickets in the UK has recently been highlighted4,31
with Ladhani et al
reporting data on 65 cases. We found the same major early peak of presentation, although Ladhani et al
reported a small additional adolescent peak with hypocalcaemic presentation. Peak presentation in winter and spring was more evident in our patient group. We reported a higher rate of x
ray changes of rickets in hypocalcaemic subjects (84%) compared with the UK study (41%). We also found that PTH was significantly higher in the hypocalcaemic subjects in our study; however six hypocalcaemic subjects did not have elevated PTH, perhaps reflecting assay or blood collection issues.
As has been noted by others,4,32
we also identified a subset of 11 cases with hyperphosphataemia, all aged less than 7 months. In some cases this had caused initial diagnostic confusion with hypoparathyroidism, since vitamin D and PTH levels were not available for up to two weeks after sampling. Each case presented with profound hypocalcaemia, hypocalcaemic seizures, and subsequently all had vitamin D levels of <20 nmol/l. In 8 of the 10 cases where PTH levels were available, PTH levels were raised (median 28 pmol/l, range 2.8–80). Suggested mechanisms for this phenomenon include refractoriness of bone to PTH after prolonged vitamin D deficiency33
and diminished response of renal cyclic adenosine monophosphate to PTH,34
which is further diminished in hypocalcaemia.35
The lower urinary excretion of phosphate noted in exclusively breast fed infants compared to formula fed infants may be a contributing factor.29
Also of note in our subjects was the great variability of 1,25‐dihydroxyvitamin D levels (when measured) as previously reported,17
highlighting its limited value for diagnosis. This most likely reflects transient peaks due to rapid conversion of 25‐hydroxyvitamin D after vitamin D intake or short periods of sunlight exposure and the short half‐life of 1,25‐dihydroxyvitamin D, with these transient effects not being exerted on bone or kidney.
The data presented in this study do not fully reflect the characteristics or prevalence of rickets in Sydney, due to incomplete ascertainment. Nevertheless the large numbers highlight the need to understand the changing demographics and public health issues associated with vitamin D deficient rickets. Maternal dietary history was not consistently recorded, and the classification of sunlight exposure is subjective. Calcium deficiency has been found to play a major role in Nigerian children with rickets, with only one third of rickets phenotype children having 25‐hydroxyvitamin D levels <30 nmol/l, and treated using both calcium and vitamin D supplementation.36
The impact of calcium intake in Australia is unclear and was not assessed in this cohort. The difficulties of 25‐hydroxyvitamin D and PTH measurement, with variation in accuracy among different assays, as well as laboratory assay experience,37
could have contributed to the inconsistent relationship between PTH and 25‐hydroxyvitamin D.
The American Academy of Pediatrics38
recently released guidelines for vitamin D intake, recommending that all infants have a minimum intake of 200 IU of vitamin D daily, beginning in the first 2 months of life and continuing through to adolescence. For infants not meeting this intake, supplementation was recommended, including all substantially breast fed infants and non‐breast fed infants who are not ingesting adequate vitamin D fortified formula or milk. Supplementation was also recommended for children and adolescents who do not get regular sunlight exposure. Despite a recognised need,39
no similar recommendations currently exist in Australia. Treatment and counselling in pregnancy was found to be inadequate in a Melbourne study, with 40% of infants aged 4–12 months found to be vitamin D deficient (25‐hydroxyvitamin D <50 mmol/l), and those breast fed more severely affected.16
We have shown a dramatic increase in the presentation of vitamin D deficient rickets to major paediatric centres in Sydney, a large, modern city with good nutritional and health standards and relatively high sunlight hours. Health practitioners need to be re‐educated about this condition and be aware of groups at risk, including other family members who are likely to have subclinical vitamin D deficiency. Infants with severe vitamin D deficiency are likely to present early with seizures and there is a subgroup of these in which hyperphosphataemia may cause initial diagnostic confusion. The public health issues have not yet been adequately addressed; consideration should be given to screening at risk immigrant groups, education programmes, and supplementation, if these increasing trends are to be reversed.