The diurnal rhythms of Ca and P metabolism

Plasma total Ca is reported to have a nadir at night and a day-time peak in men and women (see Fig. 2)⁽ Reference Greenspan, Dresner-Pollak and Parker ^{23 ,} Reference Rejnmark, Lauridsen and Vestergaard ^{24 )}. It remains unclear whether this is related to the DR of plasma albumin⁽ Reference Rejnmark, Lauridsen and Vestergaard ^{24 ,} Reference Ahmad, Hopkins and Fraser ^{25 )}. Urinary Ca (as expressed in mmol/h or as a ratio to urinary creatinine (uCa/uCr)) follows a significant DR with a night-time nadir and a day-time peak in both younger and older adults⁽ Reference Rejnmark, Lauridsen and Vestergaard ^{24 ,} Reference el-Hajj Fuleihan, Klerman and Brown ^{26 ,} Reference Calvo, Eastell and Offord ^{27 )}. Plasma P tends to follow a DR with an increase during the day, with a peak late in the evening and night and a nadir in the early morning, both in post-menopausal women⁽ Reference Rejnmark, Lauridsen and Vestergaard ^{24 )} and healthy adult men and women⁽ Reference Jubiz, Canterbury and Reiss ^{28 )}. Urinary P excretion (as measured by mmol/h or as uP/uCr), exhibits a nocturnal nadir and a day-time peak⁽ Reference Rejnmark, Lauridsen and Vestergaard ^{24 ,} Reference el-Hajj Fuleihan, Klerman and Brown ^{26 )}; this is consistent with the DR described for uCa excretion. The nocturnal decrease in renal Ca and P excretion is likely to partly reflect the biological response to nocturnal fasting by conserving minerals at the kidney level. The nocturnal decrease in urinary mineral excretion may also be associated with the DR in plasma PTH.

Fig. 2. Diurnal variation in total plasma Ca (albumin-adjusted: bold lines and unadjusted: broken line), phosphate (P) and parathyroid hormone (PTH) (change from 24 h mean, % mean and sem) in healthy post-menopausal women. P-value indicates the significance of the diurnal variation. Reproduced from⁽ Reference Ahmad, Hopkins and Fraser ^{25 )} with permission. Figure 2 was granted permission for reproduction by Copyright Clearance Center's RightsLink service by the European Journal of Endocrinology. License no.: 3213570527941.

The diurnal rhythm of parathyroid hormone

Plasma PTH concentration exhibits a well-documented DR with two peaks in healthy people, one in the afternoon/evening, and one at night (see Fig. 2)⁽ Reference Greenspan, Dresner-Pollak and Parker ^{23 ,} Reference Rejnmark, Lauridsen and Vestergaard ^{24 ,} Reference el-Hajj Fuleihan, Klerman and Brown ^{26 ,} Reference Ledger, Burritt and Kao ^{29 )}. The timing of the nocturnal peak of plasma PTH concentration corresponds to a decrease in uCa/uCr excretion and (with a time lag) to the decrease in uP/uCr⁽ Reference el-Hajj Fuleihan, Klerman and Brown ^{26 )}. This is suggestive of a physiological role for the DR of PTH in regulating renal Ca and P excretion⁽ Reference el-Hajj Fuleihan, Klerman and Brown ^{26 )}.

Studies of the pathological conditions have shown changes in the DR of PTH⁽ Reference Ahmad, Hopkins and Fraser ^{25 ,} Reference Fraser, Logue and Christie ^{30 –} Reference Fraser, Ahmad and Vora ^{32 )}. A comparative study between osteoporotic and healthy women reported a significant DR of PTH in both the groups, but with differences observed between the groups⁽ Reference Joseph, Ahmad and Ul-Haq ^{33 )}. In osteoporotic women, there was a higher 24-h mean of plasma PTH concentration with a smaller nocturnal increase, and the nocturnal peak occurred at an earlier time compared with healthy women⁽ Reference Joseph, Ahmad and Ul-Haq ^{33 )}. These findings suggest that the DR of plasma PTH may be important for overall mineral and bone metabolisms. The physiology of the DR of plasma PTH has been reviewed elsewhere in detail⁽ Reference Fraser, Ahmad and Vora ^{32 )}.

The diurnal rhythms of 1,25(OH)₂D, vitamin D binding protein and fibroblast growth factor-23

Plasma 1,25(OH)₂D and vitamin-D-binding-protein were found to have a significant DR in postmenopausal women, although the free fraction of 1,25(OH) ₂D (i.e. not bound to the vitamin-D-binding-protein) did not vary over the 24-h cycle⁽ Reference Rejnmark, Lauridsen and Vestergaard ^{24 )}. Only one study is available which investigates the DR of FGF-23 and has reported that FGF-23 did not have any significant DR in healthy children and adults and patients with X-linked hypophosphataemia, although a significant DR was observed for its biological co-factor, Klotho⁽ Reference Carpenter, Insogna and Zhang ^{34 )}.

The diurnal rhythms of bone turnover markers

Biochemical markers of bone turnover exhibit a DR, with a night-time peak and a day-time nadir⁽ Reference Greenspan, Dresner-Pollak and Parker ^{23 ,} Reference Clowes, Hannon and Yap ^{35 –} Reference Wichers, Schmidt and Bidlingmaier ^{37 )}. In a study of healthy men, the bone resorption marker, carboxy-terminal-collagen-crosslinks had a night-time peak that was 66 % greater than the 24-h mean⁽ Reference Wichers, Schmidt and Bidlingmaier ^{37 )}. The DR of the bone formation markers osteocalcin and the bone-alkaline-phosphatase exhibits less variation than the DR of bone resorption, and the amplitude is typically only 10–20 % of the 24-h mean⁽ Reference Greenspan, Dresner-Pollak and Parker ^{23 ,} Reference Gundberg, Markowitz and Mizruchi ^{38 )}; which may relate to the differences in metabolism or excretion of the markers⁽ Reference Clowes, Hannon and Yap ^{35 )}.

The DR of the bone turnover markers is partially dictated by exogenous factors; it is altered by fasting and food intake⁽ Reference Clowes, Hannon and Yap ^{35 ,} Reference Schlemmer and Hassager ^{39 ,} Reference Walsh and Henriksen ^{40 )}. It was reported that plasma concentrations of the bone resorption marker carboxy-terminal-collagen-crosslinks, and to a lesser extent the bone formation markers procollagen-type-I-N-terminal-propeptide and osteocalcin, were significantly higher after 9 h fasting compared with the fed state⁽ Reference Clowes, Hannon and Yap ^{35 )}. There are acute post-prandial changes in bone turnover that may be associated with changes in the activity of mature bone cells⁽ Reference Walsh and Henriksen ^{40 )}. Potential mediators of this response include calciotropic hormones, growth hormone, pancreatic peptides and incretin hormones. The DR of bone resorption has also been described to be modulated by the pattern of dietary Ca intake⁽ Reference Blumsohn, Herrington and Hannon ^{41 –} Reference Aerssens, Declerck and Maeyaert ^{43 )}. Further information may be found in a recent review⁽ Reference Walsh and Henriksen ^{40 )}.

Ahmad et al. reported an association between the DR of plasma concentrations of PTH and bone turnover markers; the timing of the peak concentrations of the carboxy-terminal-collagen-crosslinks and the procollagen-type-I-N-terminal-propeptide lagged behind the peak concentration of PTH by about 3 h⁽ Reference Ahmad, Hopkins and Fraser ^{25 )}. The results of this study suggest that PTH may have some regulatory role in the DR of bone resorption and formation, as reflected by the markers of the bone turnover⁽ Reference Ahmad, Hopkins and Fraser ^{25 )}, although this has not been consistently seen⁽ Reference Ledger, Burritt and Kao ^{29 )}.

Taken together, these results suggest the homoeostasis of plasma Ca at night, in the absence of Ca intake, is maintained by an enhanced bone resorption and also by an enhanced renal reabsorption of Ca⁽ Reference Bell, Williamson and Hollis ^{44 )}. This homoeostasis is in part, but not completely, mediated via a nocturnal increase in plasma PTH. Differences in DR of Ca, P and bone metabolisms between healthy individuals and patients with osteoporosis are reported⁽ Reference Fraser, Logue and Christie ^{30 ,} Reference Eastell, Calvo and Burritt ^{31 )}, particularly in PTH and uCa excretions. This indicates that they may be important for Ca balance and skeletal integrity.

Little is known about the influence of ethnicity on these DR. Differences may be expected between ethnic groups due to differences in lifestyle factors, including the timing of sleep–wake patterns, the pattern of dietary intake and total dietary intake. Differences in dietary intake and other factors associated with Ca and P metabolisms may vary considerably between ethnic groups, and will be discussed in this review.

Ethnic differences in dietary Ca and P intakes in the USA

Within the USA, ethnic groups differ in dietary Ca intake. White-Americans have a Ca intake close to the recommendations (∼900 mg/d), while African-Americans have a lower Ca intake at all stages of life, as documented in the National Health and Nutrition Examination Survey⁽ Reference Alaimo, McDowell and Briefel ^{53 )} and other studies⁽ Reference Bell, Williamson and Hollis ^{44 ,} Reference Aloia, Mikhail and Pagan ^{59 )}. African-Americans are reported to consume the same or less dietary P than White-Americans⁽ Reference Fulgoni, Nicholls and Reed ^{60 )}.

Some studies have reported greater fractional and total intestinal Ca absorption in African-Americans compared with White-American children and adolescents⁽ Reference Abrams, O'Brien and Liang ^{61 ,} Reference Braun, Palacios and Wigertz ^{62 )}. However, Bell et al. did not find any differences in fractional intestinal Ca absorption, despite the finding of lower serum 25(OH)D concentration and 24-h uCa excretion and higher serum 1,25(OH)₂D in African-Americans than in White-American adolescents⁽ Reference Bell, Yergey and Vieira ^{63 )}.

Ethnic differences in 25(OH)D in the USA

After exposure to a single standard dose of UV radiation, there is less dermal synthesis of vitamin D₃ from 7-dehydrocholesterol in darker skin because of the absorption of UVB-light by the skin pigment⁽ Reference Clemens, Adams and Henderson ^{64 )}, although the total capacity appears to be similar in African-Americans and White-American young adults when exposed to unlimited sunshine⁽ Reference Brazerol, McPhee and Mimouni ^{65 )}. Consequently, when living in temperate climates, darker skinned individuals tend to have lower plasma 25(OH)D concentrations. This is reflected in data obtained within the USA, including the National Health and Nutrition Examination Survey, where for similar amounts of UVB-containing sunshine exposure, African-Americans have lower 25(OH)D in winter and summer⁽ Reference Aloia, Mikhail and Pagan ^{59 ,} Reference Dawson-Hughes ^{66 ,} Reference Gutierrez, Farwell and Kermah ^{67 )}.

The lower plasma 25(OH)D concentration may also be partly explained by a higher BMI on average in African-Americans, as BMI is inversely associated with plasma 25(OH)D⁽ Reference Arunabh, Pollack and Yeh ^{68 )}. However, Coney et al. report that ethnic differences in plasma 25(OH)D remain after adjustment for body weight, percentage body fat and BMI⁽ Reference Coney, Demers and Dodson ^{69 )}. The lower 25(OH)D may be possibly explained partly by genetic variations in vitamin D synthesis, the vitamin-D-binding-protein and/or metabolism between ethnic groups⁽ Reference Dawson-Hughes ^{66 ,} Reference Signorello, Shi and Cai ^{70 )}.

Ethnic differences in regulatory hormones in the USA

Plasma PTH, 1,25(OH)₂D and urinary cyclic-adenosine-3′,5′-monophosphate (an indicator of renal PTH activity) have been reported to be higher in African-Americans compared with White-American adults⁽ Reference Finkelstein, Sowers and Greendale ^{71 –} Reference Bell ^{73 )}. A lower vitamin D status, in addition to a lower Ca intake, may explain these findings⁽ Reference Bell, Greene and Epstein ^{72 )}, since PTH is a primary regulator of Ca metabolism, as described earlier. The higher plasma PTH in African-Americans, however, may not lead to a similarly increased rate of bone turnover or risk of osteoporosis as it does for White-Americans. A comparative study of African-American and White-American women matched for age and weight, reported that, despite having lower plasma 25(OH)D and higher plasma PTH, African-American women have a higher bone mineral density and bone mineral content and lower bone turnover rate⁽ Reference Aloia, Mikhail and Pagan ^{59 )}. This was confirmed by other studies reporting lower concentrations of bone turnover markers in African-Americans despite a similar or higher plasma PTH as White-Americans⁽ Reference Bell, Greene and Epstein ^{72 ,} Reference Kleerekoper, Nelson and Peterson ^{74 )}. This is further underpinned by the results of a controlled PTH infusion study showing a lower rise in the markers of bone resorption in African-American compared with White-American premenopausal women in response to the same amount of infused PTH⁽ Reference Cosman, Morgan and Nieves ^{17 )}. Furthermore, histomorphometric analysis of biopsies of the iliac crest after double-tetracycline labelling showed that the bone formation rate in African-American adults was only one-third that of White men and women⁽ Reference Weinstein and Bell ^{75 )}. In addition, the relationship between plasma 25(OH)D concentration and bone outcomes differs by ethnicity; a lower plasma 25(OH)D is associated with a lower bone mineral density in White-Americans, but not African-Americans⁽ Reference Gutierrez, Farwell and Kermah ^{67 )}. Taken together, these pieces of evidence suggest that the bone resorptive response to PTH differs between these groups, and it has been suggested that African-Americans have a relative skeletal resistance to PTH⁽ Reference Gutierrez, Farwell and Kermah ^{67 )}.

Ethnic differences in renal mineral excretion in the USA

Studies comparing ethnic groups in the USA have shown that the African-American adults have lower daily uCa and uP excretions across all ages⁽ Reference Aloia, Mikhail and Pagan ^{59 ,} Reference Braun, Palacios and Wigertz ^{62 ,} Reference Bell, Greene and Epstein ^{72 ,} Reference Gutierrez, Isakova and Smith ^{76 )}. Postmenopausal African-American women excrete on average 65 mg less uCa/d and 120 mg less uP/d than White-American women⁽ Reference Taylor and Curhan ^{77 )}. In steady-state conditions of mineral ion balance, the daily urinary mineral excretion equates to net absorption from dietary sources⁽ Reference Gutierrez, Isakova and Smith ^{76 )}; accordingly, it has been speculated that the lower urinary mineral excretion among African-Americans is due to a lower intestinal absorption of Ca and P. This, however, needs to be interpreted with consideration of dietary intake. As mentioned earlier, when compared with White-Americans, African-Americans consume less dietary Ca and the same or less dietary P⁽ Reference Fulgoni, Nicholls and Reed ^{60 )}. It has been demonstrated in adolescents and adult women that lower daily uCa excretion in African-Americans is primarily determined by a higher renal Ca conservation rather than lower fractional intestinal Ca absorption⁽ Reference Bell, Yergey and Vieira ^{63 ,} Reference Dawson-Hughes, Harris and Finneran ^{78 )}. These differences cannot be fully explained by a higher plasma PTH and a 1,25(OH)₂D concentration in African-Americans. A lower 24-h Ca excretion was reported in African-Americans compared with White-American adolescent girls across a range of controlled dietary Ca intakes, and at similar concentrations of plasma 25(OH)D, 1,25(OH)₂D and PTH⁽ Reference Braun, Palacios and Wigertz ^{62 )}. This was confirmed by a study by Gutierrez et al. examining ethnic differences in postprandial urinary fractional mineral excretion between African-American and White-American adults in samples collected for 4 h following a standardised meal⁽ Reference Gutierrez, Isakova and Smith ^{76 )}. Despite similar plasma PTH and FGF-23 concentrations, African-Americans had ∼35 % lower fractional Ca excretion and ∼30 % lower postprandial fractional P excretion than White-Americans⁽ Reference Gutierrez, Isakova and Smith ^{76 )}. These pieces of evidence suggest that African-Americans have a proportionally higher renal mineral conservation than White-Americans.

Overall, there appears to be strong evidence supporting the biologically relevant ethnic differences across all aspects of Ca and P metabolism and in the concentrations and responses to the regulators between African-Americans and White-Americans. The differences described in the skeletal responsivity to PTH, the rate of bone remodelling and the differences in Ca and P retentions may be associated with ethnic differences in bone mass and fracture risk (Table 1).

Table 1. Factors associated with ethnic differences in Ca, P and bone metabolism within the USA

PTH, parathyroid hormone.

* Arrows indicate the differences compared with White-Americans.

Ethnic differences in dietary intake: The Gambia v. the UK

Dietary Ca intake in The Gambia, West Africa, is very low (200–400 mg/d)⁽ Reference Yan, Schoenmakers and Zhou ^{47 ,} Reference Jarjou, Prentice and Sawo ^{79 ,} Reference Schoenmakers, Ginty and Jarjou ^{80 )}. The main contributors to daily Ca intake are leaves, fish, locust beans, cereals, groundnuts and local salt, while milk is reported to account for only 5 % of Ca intake⁽ Reference Prentice, Laskey and Shaw ^{46 )}. In the UK, milk and milk products contribute substantially to dietary Ca intake (approximately 56 %). Daily Ca intake is generally close to recommendations (760–960 mg/d) with some regional variations^{( 52 )}. We have previously reported that the dietary Ca and Ca:P intakes were lower in rural Gambian compared with White-British adolescents and older adults from Cambridge⁽ Reference Yan, Schoenmakers and Zhou ^{47 ,} Reference Schoenmakers, Ginty and Jarjou ^{80 )}.

Ethnic differences in 25(OH)D: The Gambia v. the UK

Vitamin D status in The Gambia is generally higher than in the UK. Plasma 25(OH)D was reported to be 60–100 nmol/l in Gambian men and women throughout the year across all ages and in pregnancy⁽ Reference Prentice ^{21 ,} Reference Schoenmakers, Ginty and Jarjou ^{80 –} Reference Schoenmakers, Jarjou and Goldberg ^{83 )}. In the UK, vitamin D status undergoes seasonal variation. The UK National Diet and Nutrition Survey reported mean annual 25(OH)D concentrations as 45·6 (sd 22·6)nmol/l for men and 49·6 (sd 25·6)nmol/l for women aged 19–64 years⁽ Reference Bates, Lennox and Prentice ^{84 )}.

Ethnic differences in regulatory factors: The Gambia v. the UK

Plasma PTH and 1,25(OH)₂D concentrations are raised in Gambians compared with White-British subjects, and this is likely the result of their very low Ca intake⁽ Reference Schoenmakers, Ginty and Jarjou ^{80 ,} Reference Aspray, Yan and Prentice ^{82 ,} Reference Prentice, Shaw and Laskey ^{85 )}. A higher plasma PTH in the Gambia is found in conjunction with higher plasma concentrations of markers of osteoblast activity, with or without the concomitant higher markers of osteoclast activity⁽ Reference Yan, Schoenmakers and Zhou ^{47 ,} Reference Aspray, Yan and Prentice ^{82 )}. Therefore, it appears that the higher plasma PTH in The Gambia is associated with greater bone turnover, which is similar to the findings reported in South Africans⁽ Reference Schnitzler ^{86 )}, but is in contrast to the lower bone turnover and the reported skeletal resistance in African-Americans⁽ Reference Cosman, Morgan and Nieves ^{17 )}. These findings are confirmed by a detailed study investigating the bone response after oral-P-induced PTH secretion⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}. This study showed no proportional differences between Gambians and White-British adults in the skeletal response to a raised plasma PTH⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}, suggesting no difference in their relative skeletal sensitivity to PTH.

In White-British and other White populations, a high plasma PTH has been shown to be related to a lower hip bone mineral content⁽ Reference Yan, Zhou and Wang ^{87 )} and pathologically elevated plasma PTH is a significant risk factor for osteoporosis and fracture^{( 88 )}. In contrast, the chronically raised plasma PTH concentration that has been reported in the adults from The Gambia⁽ Reference Schoenmakers, Ginty and Jarjou ^{80 ,} Reference Aspray, Yan and Prentice ^{82 ,} Reference Prentice, Shaw and Laskey ^{85 )}, is not associated with a high incidence of fracture on a population level⁽ Reference Aspray, Prentice and Cole ^{89 )}. Schnitzler suggested that high bone turnover may remove fatigue damage and improve bone quality⁽ Reference Schnitzler ^{86 )} and is a plausible explanation for the very low fracture rates in West Africa.

Ethnic differences in renal mineral excretion: The Gambia v. the UK

There is evidence for differences in renal mineral conservation between The Gambia and the UK. Aspray et al. found that the 24-h uCa and uP outputs were both significantly lower in the rural Gambian adult women, particularly after menopause, compared with White-British women⁽ Reference Aspray, Yan and Prentice ^{82 )}. Further investigations of renal Ca handling and the influence of dietary intake in elderly men and women from the Gambia and the UK showed that the 2-h fasting uCa/uCr excretion was significantly lower in Gambian subjects. The UCa/uCr remained lower in Gambian subjects even after statistical adjustment for dietary Ca intake and for glomerular filtration rate, body weight, height and body surface area⁽ Reference Redmond, Jarjou and Palla ^{90 )}. There were also differences in the fractional excretion of Ca (i.e. the percentage of Ca filtered by the kidney which is excreted in the urine), and in the tubular maximum of Ca (i.e. the maximum renal tubular mineral reabsorption, a threshold beyond which Ca is excreted in the urine)⁽ Reference Redmond, Jarjou and Palla ^{90 )}. Similar trends were observed for uP and these differences also remained after statistical adjustment for dietary intake.

Taken together, these pieces of evidence suggest important differences in the Ca and P regulatory axes between White-British and Gambian adults, and between Gambians and African-Americans.

Ethnic differences in dietary intake: China v. the UK

The traditional Chinese diet is low in Ca because of the low consumption of milk and milk products; Ca intake comes mainly from the consumption of green vegetables, legumes, cereals and small fish⁽ Reference Zhang, Wang and Wang ^{51 ,} Reference Lau, Donnan and Barker ^{91 )}. There is also considerable geographical dietary variation within China⁽ Reference Hu, Zhao and Jia ^{48 )}. Hu et al. reported that the mean Ca intake ranged from 200 to 700 mg/d depending on the region⁽ Reference Hu, Zhao and Jia ^{48 )}. Zhang et al. reported an increasing trend in the daily intake of Ca in Chinese adults between 1991 and 2009. Despite this, the average Ca intake in 2009 was 400 and 352 mg/d for men and women, respectively⁽ Reference Zhang, Wang and Wang ^{51 )}. Other studies report Ca intakes were typically below 500 mg/d⁽ Reference Lau, Woo and Lam ^{92 ,} Reference Kruger, Ha and Todd ^{93 )}. We have previously reported that older Chinese adults in Shenyang, Northern China have lower dietary Ca and P intakes and a lower dietary Ca:P ratio compared with their White-British counterparts⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}.

Ethnic differences in 25(OH)D: China v. the UK

Zhang et al. reviewed publications measuring the plasma 25(OH)D in China in various age groups and in different areas of China⁽ Reference Zhang, Stoecklin and Eggersdorfer ^{94 )}. It was found that the vitamin D deficiency (defined as plasma 25(OH)D concentration <25 nmol/l) is observed in the Chinese population in almost all age groups and areas. For example, a high prevalence of deficiency was reported in Beijing (40°N) in the autumn and in Nanjing (latitude 31°N) during the winter months⁽ Reference Zhang, Stoecklin and Eggersdorfer ^{94 )}. In women from Nanjing, the mean plasma 25(OH)D concentrations were 22 and 32 nmol/l in the winter and the summer, respectively⁽ Reference Jiang, Xu and Pan ^{95 )}. In our studies, we have also reported significantly lower plasma 25(OH)D concentrations in the Chinese men in Shenyang (42°N) compared with their White-British counterparts in Cambridge (52°N) in late winter but not in summer⁽ Reference Yan, Zhou and Wang ^{87 )}.

The aetiology of vitamin D deficiency in China is likely to be multifactorial. At latitudes >30°N, there is little to no cutaneous synthesis of vitamin D during the winter; the length of the ‘UVB winter’ depends on the latitude and is longer further in the North⁽ Reference Engelsen ^{96 )}. In addition, there may be avoidance of skin exposure to UVB from sunshine for cultural reasons, and high levels of air pollution in some areas⁽ Reference Zhang, Stoecklin and Eggersdorfer ^{94 )}. Foods rich in vitamin D in the Chinese diet are scarce, and there is limited availability or consumption of vitamin D fortified products⁽ Reference Zhang, Stoecklin and Eggersdorfer ^{94 )}.

Ethnic differences in the regulatory factors: China v. The UK

We have previously reported that Chinese adults from Shenyang, Northern China had a higher plasma PTH concentration than White-British adults in winter months⁽ Reference Yan, Zhou and Wang ^{87 )}, although no ethnic differences were reported in data from the summer and winter combined⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}. This finding is a likely result of lower Ca intake and, in winter, a lower plasma 25(OH)D in older Chinese adults than in White-British counterparts⁽ Reference Yan, Schoenmakers and Zhou ^{47 ,} Reference Yan, Zhou and Wang ^{87 )}. The relationship between plasma PTH and 25(OH)D differed between the two ethnic groups; Chinese adults had a higher plasma PTH for a given plasma 25(OH)D concentration⁽ Reference Yan, Zhou and Wang ^{87 )}. In older White-British adults, a negative relationship between PTH and the size-adjusted bone mineral content at the femoral trochanter (after adjustment for confounders) was observed, but this relationship was not seen in older Chinese adults (Fig. 3)⁽ Reference Yan, Zhou and Wang ^{87 )}. This finding was supported by a previous study of elderly men and women from Hong Kong where the bone mineral density at the spine and the hip was not associated with plasma PTH⁽ Reference Woo, Lau and Swaminathan ^{97 )}. This suggests that older Chinese adults may have a degree of resistance to the bone resorptive effects of PTH. This was however, not confirmed by a detailed study by Yan et al., as described in the next section.

Fig. 3. The relationship between Ln parathyroid hormone (PTH) and Ln bone mineral content (BMCt) at the femoral trochanter adjusting for bone area, weight, height, age and sex in Shenyang (x) and Cambridge (•) subjects. Reprinted from^{( 88 )} with permission from Elsevier. Figure 3 was granted permission for reproduction by Copyright Clearance Center's RightsLink service by Elsevier. License no.: 3196500798854.

Ethnic differences in renal mineral excretion: China v. The UK

There are few studies available directly comparing the differences in renal excretion in these ethnic groups. The comparative results obtained from the 2-h fasting urine samples collected from older Chinese and White-British adults suggested that there were no differences in either the uCa/uCr or the uP/uCr⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}. Yan et al. investigated the potential skeletal resistance to PTH in older Chinese adults compared with older White-British adults by conducting a 5-d oral-P loading study to stimulate PTH secretion⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}. No evidence was found for the differences in the skeletal response to PTH and the results did not support the hypothesis of skeletal resistance to PTH in older Chinese adults compared with older British adults. However, a potentially important difference in the renal response to PTH was found, which was greater in the Chinese group, resulting in more rapid P clearance compared with White-British⁽ Reference Yan, Schoenmakers and Zhou ^{47 )}.